Mapping the expression of transient receptor potential channels across murine placental development
Cell Mol Life Sci. 2021 Apr 21. doi: 10.1007/s00018-021-03837-3. Online ahead of print.ABSTRACTTransient receptor potential (TRP) channels play prominent roles in ion homeostasis by their ability to control cation influx. Mouse placentation is governed by the processes of trophoblast proliferation, invasion, differentiation, and fusion, all of which require calcium signaling. Although certain TRP channels have been shown to contribute to maternal-fetal transport of magnesium and calcium, a role for TRP channels in specific trophoblast functions has been disregarded. Using qRT-PCR and in situ hybridisation, the spatio-tempo...
Source: Cellular and Molecular Life Sciences : CMLS - April 22, 2021 Category: Cytology Authors: Katrien De Clercq Vicente P érez-García Rieta Van Bree Federica Pollastro Karen Peeraer Thomas Voets Joris Vriens Source Type: research

G1-phase progression in pluripotent stem cells
Cell Mol Life Sci. 2021 Apr 21. doi: 10.1007/s00018-021-03797-8. Online ahead of print.ABSTRACTDuring early embryonic development both the rapid increase in cell number and the expression of genes that control developmental decisions are tightly regulated. Accumulating evidence has indicated that these two seemingly independent processes are mechanistically intertwined. The picture that emerges from studies on the cell cycle of embryonic stem cells is one in which proteins that promote cell cycle progression prevent differentiation and vice versa. Here, we review which transcription factors and signalling pathways play a r...
Source: Cellular and Molecular Life Sciences : CMLS - April 22, 2021 Category: Cytology Authors: Menno Ter Huurne Hendrik G Stunnenberg Source Type: research

Follicular helper T cells: potential therapeutic targets in rheumatoid arthritis
Cell Mol Life Sci. 2021 Apr 20. doi: 10.1007/s00018-021-03839-1. Online ahead of print.ABSTRACTRheumatoid arthritis (RA) is a chronic autoimmune disease with joint and systemic inflammation that is accompanied by the production of autoantibodies, such as rheumatoid factor and anti-cyclic citrullinated peptide (anti-CCP) antibodies. Follicular helper T (Tfh) cells, which are a subset of CD4+ T cells, facilitate germinal center (GC) reactions by providing signals required for high-affinity antibody production and the generation of long-lived antibody-secreting plasma cells. Uncontrolled expansion of Tfh cells is observed in ...
Source: Cellular and Molecular Life Sciences : CMLS - April 21, 2021 Category: Cytology Authors: Jian Lu Jing Wu Xueli Xia Huiyong Peng Shengjun Wang Source Type: research

Follicular helper T cells: potential therapeutic targets in rheumatoid arthritis
Cell Mol Life Sci. 2021 Apr 20. doi: 10.1007/s00018-021-03839-1. Online ahead of print.ABSTRACTRheumatoid arthritis (RA) is a chronic autoimmune disease with joint and systemic inflammation that is accompanied by the production of autoantibodies, such as rheumatoid factor and anti-cyclic citrullinated peptide (anti-CCP) antibodies. Follicular helper T (Tfh) cells, which are a subset of CD4+ T cells, facilitate germinal center (GC) reactions by providing signals required for high-affinity antibody production and the generation of long-lived antibody-secreting plasma cells. Uncontrolled expansion of Tfh cells is observed in ...
Source: Cellular and Molecular Life Sciences : CMLS - April 21, 2021 Category: Cytology Authors: Jian Lu Jing Wu Xueli Xia Huiyong Peng Shengjun Wang Source Type: research

Mechanisms underlying pre- and postnatal development of the vomeronasal organ
Cell Mol Life Sci. 2021 Apr 19. doi: 10.1007/s00018-021-03829-3. Online ahead of print.ABSTRACTThe vomeronasal organ (VNO) is sensory organ located in the ventral region of the nasal cavity in rodents. The VNO develops from the olfactory placode during the secondary invagination of olfactory pit. The embryonic vomeronasal structure appears as a neurogenic area where migratory neuronal populations like endocrine gonadotropin-releasing hormone-1 (GnRH-1) neurons form. Even though embryonic vomeronasal structures are conserved across most vertebrate species, many species including humans do not have a functional VNO after bir...
Source: Cellular and Molecular Life Sciences : CMLS - April 19, 2021 Category: Cytology Authors: Raghu Ram Katreddi Paolo E Forni Source Type: research

Mechanisms in cochlear hair cell mechano-electrical transduction for acquisition of sound frequency and intensity
Cell Mol Life Sci. 2021 Apr 19. doi: 10.1007/s00018-021-03840-8. Online ahead of print.ABSTRACTSound signals are acquired and digitized in the cochlea by the hair cells that further transmit the coded information to the central auditory pathways. Any defect in hair cell function may induce problems in the auditory system and hearing-based brain function. In the past 2 decades, our understanding of auditory transduction has been substantially deepened because of advances in molecular, structural, and functional studies. Results from these experiments can be perfectly embedded in the previously established profile from anato...
Source: Cellular and Molecular Life Sciences : CMLS - April 19, 2021 Category: Cytology Authors: Shuang Liu Shufeng Wang Linzhi Zou Wei Xiong Source Type: research

Mechanisms underlying pre- and postnatal development of the vomeronasal organ
Cell Mol Life Sci. 2021 Apr 19. doi: 10.1007/s00018-021-03829-3. Online ahead of print.ABSTRACTThe vomeronasal organ (VNO) is sensory organ located in the ventral region of the nasal cavity in rodents. The VNO develops from the olfactory placode during the secondary invagination of olfactory pit. The embryonic vomeronasal structure appears as a neurogenic area where migratory neuronal populations like endocrine gonadotropin-releasing hormone-1 (GnRH-1) neurons form. Even though embryonic vomeronasal structures are conserved across most vertebrate species, many species including humans do not have a functional VNO after bir...
Source: Cellular and Molecular Life Sciences : CMLS - April 19, 2021 Category: Cytology Authors: Raghu Ram Katreddi Paolo E Forni Source Type: research

Mechanisms in cochlear hair cell mechano-electrical transduction for acquisition of sound frequency and intensity
Cell Mol Life Sci. 2021 Apr 19. doi: 10.1007/s00018-021-03840-8. Online ahead of print.ABSTRACTSound signals are acquired and digitized in the cochlea by the hair cells that further transmit the coded information to the central auditory pathways. Any defect in hair cell function may induce problems in the auditory system and hearing-based brain function. In the past 2 decades, our understanding of auditory transduction has been substantially deepened because of advances in molecular, structural, and functional studies. Results from these experiments can be perfectly embedded in the previously established profile from anato...
Source: Cellular and Molecular Life Sciences : CMLS - April 19, 2021 Category: Cytology Authors: Shuang Liu Shufeng Wang Linzhi Zou Wei Xiong Source Type: research

Role and mechanisms of autophagy in lung metabolism and repair
Cell Mol Life Sci. 2021 Apr 17. doi: 10.1007/s00018-021-03841-7. Online ahead of print.ABSTRACTMammalian lungs are metabolically active organs that frequently encounter environmental insults. Stress responses elicit protective autophagy in epithelial barrier cells and the supportive niche. Autophagy promotes the recycling of damaged intracellular organelles, denatured proteins, and other biological macromolecules for reuse as components required for lung cell survival. Autophagy, usually induced by metabolic defects, regulates cellular metabolism. Autophagy is a major adaptive response that protects cells and organisms fro...
Source: Cellular and Molecular Life Sciences : CMLS - April 17, 2021 Category: Cytology Authors: Xue Li Fuxiaonan Zhao An Wang Peiyong Cheng Huaiyong Chen Source Type: research

A β1-16 controls synaptic vesicle pools at excitatory synapses via cholinergic modulation of synapsin phosphorylation
Cell Mol Life Sci. 2021 Apr 17. doi: 10.1007/s00018-021-03835-5. Online ahead of print.ABSTRACTAmyloid beta (Aβ) is linked to the pathology of Alzheimer's disease (AD). At physiological concentrations, Aβ was proposed to enhance neuroplasticity and memory formation by increasing the neurotransmitter release from presynapse. However, the exact mechanisms underlying this presynaptic effect as well as specific contribution of endogenously occurring Aβ isoforms remain unclear. Here, we demonstrate that Aβ1-42 and Aβ1-16, but not Aβ17-42, increased size of the recycling pool of synaptic vesicles (S...
Source: Cellular and Molecular Life Sciences : CMLS - April 17, 2021 Category: Cytology Authors: Daniela Anni Eva-Maria Weiss Debarpan Guhathakurta Yagiz Enes Akdas Julia Klueva Stefanie Zeitler Maria Andres-Alonso Tobias Huth Anna Fejtova Source Type: research

Role and mechanisms of autophagy in lung metabolism and repair
Cell Mol Life Sci. 2021 Apr 17. doi: 10.1007/s00018-021-03841-7. Online ahead of print.ABSTRACTMammalian lungs are metabolically active organs that frequently encounter environmental insults. Stress responses elicit protective autophagy in epithelial barrier cells and the supportive niche. Autophagy promotes the recycling of damaged intracellular organelles, denatured proteins, and other biological macromolecules for reuse as components required for lung cell survival. Autophagy, usually induced by metabolic defects, regulates cellular metabolism. Autophagy is a major adaptive response that protects cells and organisms fro...
Source: Cellular and Molecular Life Sciences : CMLS - April 17, 2021 Category: Cytology Authors: Xue Li Fuxiaonan Zhao An Wang Peiyong Cheng Huaiyong Chen Source Type: research

A β1-16 controls synaptic vesicle pools at excitatory synapses via cholinergic modulation of synapsin phosphorylation
Cell Mol Life Sci. 2021 Apr 17. doi: 10.1007/s00018-021-03835-5. Online ahead of print.ABSTRACTAmyloid beta (Aβ) is linked to the pathology of Alzheimer's disease (AD). At physiological concentrations, Aβ was proposed to enhance neuroplasticity and memory formation by increasing the neurotransmitter release from presynapse. However, the exact mechanisms underlying this presynaptic effect as well as specific contribution of endogenously occurring Aβ isoforms remain unclear. Here, we demonstrate that Aβ1-42 and Aβ1-16, but not Aβ17-42, increased size of the recycling pool of synaptic vesicles (S...
Source: Cellular and Molecular Life Sciences : CMLS - April 17, 2021 Category: Cytology Authors: Daniela Anni Eva-Maria Weiss Debarpan Guhathakurta Yagiz Enes Akdas Julia Klueva Stefanie Zeitler Maria Andres-Alonso Tobias Huth Anna Fejtova Source Type: research

Moonlighting of mitotic regulators in cilium disassembly
Cell Mol Life Sci. 2021 Apr 15. doi: 10.1007/s00018-021-03827-5. Online ahead of print.ABSTRACTCorrect timing of cellular processes is essential during embryological development and to maintain the balance between healthy proliferation and tumour formation. Assembly and disassembly of the primary cilium, the cell's sensory signalling organelle, are linked to cell cycle timing in the same manner as spindle pole assembly and chromosome segregation. Mitotic processes, ciliary assembly, and ciliary disassembly depend on the centrioles as microtubule-organizing centres (MTOC) to regulate polymerizing and depolymerizing microtub...
Source: Cellular and Molecular Life Sciences : CMLS - April 16, 2021 Category: Cytology Authors: Cenna Doornbos Ronald Roepman Source Type: research

The relationship between muscle stem cells and motor neurons
Cell Mol Life Sci. 2021 Apr 16. doi: 10.1007/s00018-021-03838-2. Online ahead of print.ABSTRACTNeuromuscular system is constituted of multi-fibrillar muscles, tendons, motor neurons and associated muscle stem cells. Stereotyped pattern of muscle innervation and muscle-specific interactions with tendon cells suggest that neuromuscular system develops in a coordinated way. Remarkably, upon regeneration, coordinated assembly of all neuromuscular components is also critical to rebuild functional muscle. Thus, to ensure muscle function, the neuromuscular system components need to interact both during development and regeneratio...
Source: Cellular and Molecular Life Sciences : CMLS - April 16, 2021 Category: Cytology Authors: Monika Zmojdzian Krzysztof Jagla Source Type: research

Moonlighting of mitotic regulators in cilium disassembly
Cell Mol Life Sci. 2021 Apr 15. doi: 10.1007/s00018-021-03827-5. Online ahead of print.ABSTRACTCorrect timing of cellular processes is essential during embryological development and to maintain the balance between healthy proliferation and tumour formation. Assembly and disassembly of the primary cilium, the cell's sensory signalling organelle, are linked to cell cycle timing in the same manner as spindle pole assembly and chromosome segregation. Mitotic processes, ciliary assembly, and ciliary disassembly depend on the centrioles as microtubule-organizing centres (MTOC) to regulate polymerizing and depolymerizing microtub...
Source: Cellular and Molecular Life Sciences : CMLS - April 16, 2021 Category: Cytology Authors: Cenna Doornbos Ronald Roepman Source Type: research

The relationship between muscle stem cells and motor neurons
Cell Mol Life Sci. 2021 Apr 16. doi: 10.1007/s00018-021-03838-2. Online ahead of print.ABSTRACTNeuromuscular system is constituted of multi-fibrillar muscles, tendons, motor neurons and associated muscle stem cells. Stereotyped pattern of muscle innervation and muscle-specific interactions with tendon cells suggest that neuromuscular system develops in a coordinated way. Remarkably, upon regeneration, coordinated assembly of all neuromuscular components is also critical to rebuild functional muscle. Thus, to ensure muscle function, the neuromuscular system components need to interact both during development and regeneratio...
Source: Cellular and Molecular Life Sciences : CMLS - April 16, 2021 Category: Cytology Authors: Monika Zmojdzian Krzysztof Jagla Source Type: research

The Ku complex: recent advances and emerging roles outside of non-homologous end-joining
Cell Mol Life Sci. 2021 Apr 15. doi: 10.1007/s00018-021-03801-1. Online ahead of print.ABSTRACTSince its discovery in 1981, the Ku complex has been extensively studied under multiple cellular contexts, with most work focusing on Ku in terms of its essential role in non-homologous end-joining (NHEJ). In this process, Ku is well-known as the DNA-binding subunit for DNA-PK, which is central to the NHEJ repair process. However, in addition to the extensive study of Ku's role in DNA repair, Ku has also been implicated in various other cellular processes including transcription, the DNA damage response, DNA replication, telomere...
Source: Cellular and Molecular Life Sciences : CMLS - April 15, 2021 Category: Cytology Authors: Sanna Abbasi Gursimran Parmar Rachel D Kelly Nileeka Balasuriya Caroline Schild-Poulter Source Type: research

The Ku complex: recent advances and emerging roles outside of non-homologous end-joining
Cell Mol Life Sci. 2021 Apr 15. doi: 10.1007/s00018-021-03801-1. Online ahead of print.ABSTRACTSince its discovery in 1981, the Ku complex has been extensively studied under multiple cellular contexts, with most work focusing on Ku in terms of its essential role in non-homologous end-joining (NHEJ). In this process, Ku is well-known as the DNA-binding subunit for DNA-PK, which is central to the NHEJ repair process. However, in addition to the extensive study of Ku's role in DNA repair, Ku has also been implicated in various other cellular processes including transcription, the DNA damage response, DNA replication, telomere...
Source: Cellular and Molecular Life Sciences : CMLS - April 15, 2021 Category: Cytology Authors: Sanna Abbasi Gursimran Parmar Rachel D Kelly Nileeka Balasuriya Caroline Schild-Poulter Source Type: research

Compartmentalized replication organelle of flavivirus at the ER and the factors involved
Cell Mol Life Sci. 2021 Apr 12:1-16. doi: 10.1007/s00018-021-03834-6. Online ahead of print.ABSTRACTFlaviviruses are positive-sense single-stranded RNA viruses that pose a considerable threat to human health. Flaviviruses replicate in compartmentalized replication organelles derived from the host endoplasmic reticulum (ER). The characteristic architecture of flavivirus replication organelles includes invaginated vesicle packets and convoluted membrane structures. Multiple factors, including both viral proteins and host factors, contribute to the biogenesis of the flavivirus replication organelle. Several viral nonstructura...
Source: Cellular and Molecular Life Sciences : CMLS - April 13, 2021 Category: Cytology Authors: Yali Ci Lei Shi Source Type: research

Cytokine signaling convergence regulates the microglial state transition in Alzheimer's disease
Cell Mol Life Sci. 2021 Apr 13. doi: 10.1007/s00018-021-03810-0. Online ahead of print.ABSTRACTGenetic analyses have revealed the pivotal contribution of microglial dysfunctions to the pathogenesis of Alzheimer's disease (AD). Along AD progression, the accumulation of danger-associated molecular patterns (DAMPs) including beta-amyloid and hyperphosphorylated tau continuously stimulates microglia, which results in their chronic activation. Chronically activated microglia secrete excessive pro-inflammatory cytokines, which further regulate microglial responses towards DAMPs. This has spurred longstanding interest in targetin...
Source: Cellular and Molecular Life Sciences : CMLS - April 13, 2021 Category: Cytology Authors: Shun-Fat Lau Amy K Y Fu Nancy Y Ip Source Type: research

Compartmentalized replication organelle of flavivirus at the ER and the factors involved
Cell Mol Life Sci. 2021 Apr 12:1-16. doi: 10.1007/s00018-021-03834-6. Online ahead of print.ABSTRACTFlaviviruses are positive-sense single-stranded RNA viruses that pose a considerable threat to human health. Flaviviruses replicate in compartmentalized replication organelles derived from the host endoplasmic reticulum (ER). The characteristic architecture of flavivirus replication organelles includes invaginated vesicle packets and convoluted membrane structures. Multiple factors, including both viral proteins and host factors, contribute to the biogenesis of the flavivirus replication organelle. Several viral nonstructura...
Source: Cellular and Molecular Life Sciences : CMLS - April 13, 2021 Category: Cytology Authors: Yali Ci Lei Shi Source Type: research

Cytokine signaling convergence regulates the microglial state transition in Alzheimer's disease
Cell Mol Life Sci. 2021 Apr 13. doi: 10.1007/s00018-021-03810-0. Online ahead of print.ABSTRACTGenetic analyses have revealed the pivotal contribution of microglial dysfunctions to the pathogenesis of Alzheimer's disease (AD). Along AD progression, the accumulation of danger-associated molecular patterns (DAMPs) including beta-amyloid and hyperphosphorylated tau continuously stimulates microglia, which results in their chronic activation. Chronically activated microglia secrete excessive pro-inflammatory cytokines, which further regulate microglial responses towards DAMPs. This has spurred longstanding interest in targetin...
Source: Cellular and Molecular Life Sciences : CMLS - April 13, 2021 Category: Cytology Authors: Shun-Fat Lau Amy K Y Fu Nancy Y Ip Source Type: research

Pitx genes in development and disease
Cell Mol Life Sci. 2021 Apr 12. doi: 10.1007/s00018-021-03833-7. Online ahead of print.ABSTRACTHomeobox genes encode sequence-specific transcription factors (SSTFs) that recognize specific DNA sequences and regulate organogenesis in all eukaryotes. They are essential in specifying spatial and temporal cell identity and as a result, their mutations often cause severe developmental defects. Pitx genes belong to the PRD class of the highly evolutionary conserved homeobox genes in all animals. Vertebrates possess three Pitx paralogs, Pitx1, Pitx2, and Pitx3 while non-vertebrates have only one Pitx gene. The ancient role of reg...
Source: Cellular and Molecular Life Sciences : CMLS - April 12, 2021 Category: Cytology Authors: Thai Q Tran Chrissa Kioussi Source Type: research

Alzheimer's pathogenic mechanisms and underlying sex difference
Cell Mol Life Sci. 2021 Apr 12. doi: 10.1007/s00018-021-03830-w. Online ahead of print.ABSTRACTAD is a neurodegenerative disease, and its frequency is often reported to be higher for women than men: almost two-thirds of patients with AD are women. One prevailing view is that women live longer than men on average of 4.5 years, plus there are more women aged 85 years or older than men in most global subpopulations; and older age is the greatest risk factor for AD. However, the differences in the actual risk of developing AD for men and women of the same age is difficult to assess, and the findings have been mixed. An increas...
Source: Cellular and Molecular Life Sciences : CMLS - April 12, 2021 Category: Cytology Authors: Donghui Zhu Axel Montagne Zhen Zhao Source Type: research

Pitx genes in development and disease
Cell Mol Life Sci. 2021 Apr 12. doi: 10.1007/s00018-021-03833-7. Online ahead of print.ABSTRACTHomeobox genes encode sequence-specific transcription factors (SSTFs) that recognize specific DNA sequences and regulate organogenesis in all eukaryotes. They are essential in specifying spatial and temporal cell identity and as a result, their mutations often cause severe developmental defects. Pitx genes belong to the PRD class of the highly evolutionary conserved homeobox genes in all animals. Vertebrates possess three Pitx paralogs, Pitx1, Pitx2, and Pitx3 while non-vertebrates have only one Pitx gene. The ancient role of reg...
Source: Cellular and Molecular Life Sciences : CMLS - April 12, 2021 Category: Cytology Authors: Thai Q Tran Chrissa Kioussi Source Type: research

Alzheimer's pathogenic mechanisms and underlying sex difference
Cell Mol Life Sci. 2021 Apr 12. doi: 10.1007/s00018-021-03830-w. Online ahead of print.ABSTRACTAD is a neurodegenerative disease, and its frequency is often reported to be higher for women than men: almost two-thirds of patients with AD are women. One prevailing view is that women live longer than men on average of 4.5 years, plus there are more women aged 85 years or older than men in most global subpopulations; and older age is the greatest risk factor for AD. However, the differences in the actual risk of developing AD for men and women of the same age is difficult to assess, and the findings have been mixed. An increas...
Source: Cellular and Molecular Life Sciences : CMLS - April 12, 2021 Category: Cytology Authors: Donghui Zhu Axel Montagne Zhen Zhao Source Type: research

Molecular and neural mechanisms regulating sexual motivation of virgin female Drosophila
Cell Mol Life Sci. 2021 Apr 10. doi: 10.1007/s00018-021-03820-y. Online ahead of print.ABSTRACTDuring courtship, multiple information sources are integrated in the brain to reach a final decision, i.e., whether or not to mate. The brain functions for this complex behavior can be investigated by genetically manipulating genes and neurons, and performing anatomical, physiological, and behavioral analyses. Drosophila is a powerful model experimental system for such studies, which need to be integrated from molecular and cellular levels to the behavioral level, and has enabled pioneering research to be conducted. In male flies...
Source: Cellular and Molecular Life Sciences : CMLS - April 10, 2021 Category: Cytology Authors: Hiroshi Ishimoto Azusa Kamikouchi Source Type: research

Immune cells lacking Y chromosome show dysregulation of autosomal gene expression
Cell Mol Life Sci. 2021 Apr 10. doi: 10.1007/s00018-021-03822-w. Online ahead of print.ABSTRACTEpidemiological investigations show that mosaic loss of chromosome Y (LOY) in leukocytes is associated with earlier mortality and morbidity from many diseases in men. LOY is the most common acquired mutation and is associated with aberrant clonal expansion of cells, yet it remains unclear whether this mosaicism exerts a direct physiological effect. We studied DNA and RNA from leukocytes in sorted- and single-cells in vivo and in vitro. DNA analyses of sorted cells showed that men diagnosed with Alzheimer's disease was primarily a...
Source: Cellular and Molecular Life Sciences : CMLS - April 10, 2021 Category: Cytology Authors: Jan P Dumanski Jonatan Halvardson Hanna Davies Edyta Rychlicka-Buniowska Jonas Mattisson Behrooz Torabi Moghadam Noemi Nagy Kazimierz W ęglarczyk Karolina Bukowska-Strakova Marcus Danielsson Pawe ł Olszewski Arkadiusz Piotrowski Erin Oerton Aleksandra A Source Type: research

Molecular and neural mechanisms regulating sexual motivation of virgin female Drosophila
Cell Mol Life Sci. 2021 Apr 10. doi: 10.1007/s00018-021-03820-y. Online ahead of print.ABSTRACTDuring courtship, multiple information sources are integrated in the brain to reach a final decision, i.e., whether or not to mate. The brain functions for this complex behavior can be investigated by genetically manipulating genes and neurons, and performing anatomical, physiological, and behavioral analyses. Drosophila is a powerful model experimental system for such studies, which need to be integrated from molecular and cellular levels to the behavioral level, and has enabled pioneering research to be conducted. In male flies...
Source: Cellular and Molecular Life Sciences : CMLS - April 10, 2021 Category: Cytology Authors: Hiroshi Ishimoto Azusa Kamikouchi Source Type: research

Immune cells lacking Y chromosome show dysregulation of autosomal gene expression
Cell Mol Life Sci. 2021 Apr 10. doi: 10.1007/s00018-021-03822-w. Online ahead of print.ABSTRACTEpidemiological investigations show that mosaic loss of chromosome Y (LOY) in leukocytes is associated with earlier mortality and morbidity from many diseases in men. LOY is the most common acquired mutation and is associated with aberrant clonal expansion of cells, yet it remains unclear whether this mosaicism exerts a direct physiological effect. We studied DNA and RNA from leukocytes in sorted- and single-cells in vivo and in vitro. DNA analyses of sorted cells showed that men diagnosed with Alzheimer's disease was primarily a...
Source: Cellular and Molecular Life Sciences : CMLS - April 10, 2021 Category: Cytology Authors: Jan P Dumanski Jonatan Halvardson Hanna Davies Edyta Rychlicka-Buniowska Jonas Mattisson Behrooz Torabi Moghadam Noemi Nagy Kazimierz W ęglarczyk Karolina Bukowska-Strakova Marcus Danielsson Pawe ł Olszewski Arkadiusz Piotrowski Erin Oerton Aleksandra A Source Type: research

TSC-insensitive Rheb mutations induce oncogenic transformation through a combination of constitutively active mTORC1 signalling and proteome remodelling
Cell Mol Life Sci. 2021 Apr 8. doi: 10.1007/s00018-021-03825-7. Online ahead of print.ABSTRACTThe mechanistic target of rapamycin complex 1 (mTORC1) is an important regulator of cellular metabolism that is commonly hyperactivated in cancer. Recent cancer genome screens have identified multiple mutations in Ras-homolog enriched in brain (Rheb), the primary activator of mTORC1 that might act as driver oncogenes by causing hyperactivation of mTORC1. Here, we show that a number of recurrently occurring Rheb mutants drive hyperactive mTORC1 signalling through differing levels of insensitivity to the primary inactivator of Rheb,...
Source: Cellular and Molecular Life Sciences : CMLS - April 9, 2021 Category: Cytology Authors: Jianling Xie Stuart P De Poi Sean J Humphrey Leanne K Hein John B Bruning Wenru Pan Luke A Selth Timothy J Sargeant Christopher G Proud Source Type: research

SUMOylation modulates the stability and function of PI3K-p110 β
Cell Mol Life Sci. 2021 Apr 8. doi: 10.1007/s00018-021-03826-6. Online ahead of print.ABSTRACTClass I PI3K are heterodimers composed of a p85 regulatory subunit and a p110 catalytic subunit involved in multiple cellular functions. Recently, the catalytic subunit p110β has emerged as a class I PI3K isoform playing a major role in tumorigenesis. Understanding its regulation is crucial for the control of the PI3K pathway in p110β-driven cancers. Here we sought to evaluate the putative regulation of p110β by SUMO. Our data show that p110β can be modified by SUMO1 and SUMO2 in vitro, in transfected cells and...
Source: Cellular and Molecular Life Sciences : CMLS - April 9, 2021 Category: Cytology Authors: Ahmed El Motiam Carlos F de la Cruz-Herrera Santiago Vidal Roc ío Seoane Maite Baz-Mart ínez Yanis H Bouzaher Emilio Lecona Mariano Esteban Manuel S Rodr íguez Anxo Vidal Manuel Collado Carmen Rivas Source Type: research

Epigenetic regulations in mammalian spermatogenesis: RNA-m < sup > 6 < /sup > A modification and beyond
Cell Mol Life Sci. 2021 Apr 9. doi: 10.1007/s00018-021-03823-9. Online ahead of print.ABSTRACTEmerging evidence shows that m6A, one of the most abundant RNA modifications in mammals, is involved in the entire process of spermatogenesis, including mitosis, meiosis, and spermiogenesis. "Writers" catalyze m6A formation on stage-specific transcripts during male germline development, while "erasers" remove m6A modification to maintain a balance between methylation and demethylation. The different functions of RNA-m6A transcripts depend on their recognition by "readers". m6A modification mediates RN...
Source: Cellular and Molecular Life Sciences : CMLS - April 9, 2021 Category: Cytology Authors: Yiqian Gui Shuiqiao Yuan Source Type: research

TSC-insensitive Rheb mutations induce oncogenic transformation through a combination of constitutively active mTORC1 signalling and proteome remodelling
Cell Mol Life Sci. 2021 Apr 8. doi: 10.1007/s00018-021-03825-7. Online ahead of print.ABSTRACTThe mechanistic target of rapamycin complex 1 (mTORC1) is an important regulator of cellular metabolism that is commonly hyperactivated in cancer. Recent cancer genome screens have identified multiple mutations in Ras-homolog enriched in brain (Rheb), the primary activator of mTORC1 that might act as driver oncogenes by causing hyperactivation of mTORC1. Here, we show that a number of recurrently occurring Rheb mutants drive hyperactive mTORC1 signalling through differing levels of insensitivity to the primary inactivator of Rheb,...
Source: Cellular and Molecular Life Sciences : CMLS - April 9, 2021 Category: Cytology Authors: Jianling Xie Stuart P De Poi Sean J Humphrey Leanne K Hein John B Bruning Wenru Pan Luke A Selth Timothy J Sargeant Christopher G Proud Source Type: research

SUMOylation modulates the stability and function of PI3K-p110 β
Cell Mol Life Sci. 2021 Apr 8. doi: 10.1007/s00018-021-03826-6. Online ahead of print.ABSTRACTClass I PI3K are heterodimers composed of a p85 regulatory subunit and a p110 catalytic subunit involved in multiple cellular functions. Recently, the catalytic subunit p110β has emerged as a class I PI3K isoform playing a major role in tumorigenesis. Understanding its regulation is crucial for the control of the PI3K pathway in p110β-driven cancers. Here we sought to evaluate the putative regulation of p110β by SUMO. Our data show that p110β can be modified by SUMO1 and SUMO2 in vitro, in transfected cells and...
Source: Cellular and Molecular Life Sciences : CMLS - April 9, 2021 Category: Cytology Authors: Ahmed El Motiam Carlos F de la Cruz-Herrera Santiago Vidal Roc ío Seoane Maite Baz-Mart ínez Yanis H Bouzaher Emilio Lecona Mariano Esteban Manuel S Rodr íguez Anxo Vidal Manuel Collado Carmen Rivas Source Type: research

Epigenetic regulations in mammalian spermatogenesis: RNA-m < sup > 6 < /sup > A modification and beyond
Cell Mol Life Sci. 2021 Apr 9. doi: 10.1007/s00018-021-03823-9. Online ahead of print.ABSTRACTEmerging evidence shows that m6A, one of the most abundant RNA modifications in mammals, is involved in the entire process of spermatogenesis, including mitosis, meiosis, and spermiogenesis. "Writers" catalyze m6A formation on stage-specific transcripts during male germline development, while "erasers" remove m6A modification to maintain a balance between methylation and demethylation. The different functions of RNA-m6A transcripts depend on their recognition by "readers". m6A modification mediates RN...
Source: Cellular and Molecular Life Sciences : CMLS - April 9, 2021 Category: Cytology Authors: Yiqian Gui Shuiqiao Yuan Source Type: research

Manifold role of ubiquitin in Helicobacter pylori infection and gastric cancer
Cell Mol Life Sci. 2021 Apr 7. doi: 10.1007/s00018-021-03816-8. Online ahead of print.ABSTRACTInfection with H. pylori induces a strong host cellular response represented by induction of a set of molecular signaling pathways, expression of proinflammatory cytokines and changes in proliferation. Chronic infection and inflammation accompanied by secretory dysfunction can result in the development of gastric metaplasia and gastric cancer. Currently, it has been determined that the regulation of many cellular processes involves ubiquitinylation of molecular effectors. The binding of ubiquitin allows the substrate to undergo a ...
Source: Cellular and Molecular Life Sciences : CMLS - April 7, 2021 Category: Cytology Authors: Olga Sokolova Michael Naumann Source Type: research

Therapeutic aspects of cell signaling and communication in Duchenne muscular dystrophy
Cell Mol Life Sci. 2021 Apr 7. doi: 10.1007/s00018-021-03821-x. Online ahead of print.ABSTRACTDuchenne muscular dystrophy (DMD) is a devastating chromosome X-linked disease that manifests predominantly in progressive skeletal muscle wasting and dysfunctions in the heart and diaphragm. Approximately 1/5000 boys and 1/50,000,000 girls suffer from DMD, and to date, the disease is incurable and leads to premature death. This phenotypic severity is due to mutations in the DMD gene, which result in the absence of functional dystrophin protein. Initially, dystrophin was thought to be a force transducer; however, it is now conside...
Source: Cellular and Molecular Life Sciences : CMLS - April 7, 2021 Category: Cytology Authors: Alicja Starosta Patryk Konieczny Source Type: research

Manifold role of ubiquitin in Helicobacter pylori infection and gastric cancer
Cell Mol Life Sci. 2021 Apr 7. doi: 10.1007/s00018-021-03816-8. Online ahead of print.ABSTRACTInfection with H. pylori induces a strong host cellular response represented by induction of a set of molecular signaling pathways, expression of proinflammatory cytokines and changes in proliferation. Chronic infection and inflammation accompanied by secretory dysfunction can result in the development of gastric metaplasia and gastric cancer. Currently, it has been determined that the regulation of many cellular processes involves ubiquitinylation of molecular effectors. The binding of ubiquitin allows the substrate to undergo a ...
Source: Cellular and Molecular Life Sciences : CMLS - April 7, 2021 Category: Cytology Authors: Olga Sokolova Michael Naumann Source Type: research

Therapeutic aspects of cell signaling and communication in Duchenne muscular dystrophy
Cell Mol Life Sci. 2021 Apr 7. doi: 10.1007/s00018-021-03821-x. Online ahead of print.ABSTRACTDuchenne muscular dystrophy (DMD) is a devastating chromosome X-linked disease that manifests predominantly in progressive skeletal muscle wasting and dysfunctions in the heart and diaphragm. Approximately 1/5000 boys and 1/50,000,000 girls suffer from DMD, and to date, the disease is incurable and leads to premature death. This phenotypic severity is due to mutations in the DMD gene, which result in the absence of functional dystrophin protein. Initially, dystrophin was thought to be a force transducer; however, it is now conside...
Source: Cellular and Molecular Life Sciences : CMLS - April 7, 2021 Category: Cytology Authors: Alicja Starosta Patryk Konieczny Source Type: research

Revisiting the role of mitochondria in spinal muscular atrophy
Cell Mol Life Sci. 2021 Apr 5. doi: 10.1007/s00018-021-03819-5. Online ahead of print.ABSTRACTSpinal muscular atrophy (SMA) is an autosomal recessive motor neuron disease of variable clinical severity that is caused by mutations in the survival motor neuron 1 (SMN1) gene. Despite its name, SMN is a ubiquitous protein that functions within and outside the nervous system and has multiple cellular roles in transcription, translation, and proteostatic mechanisms. Encouragingly, several SMN-directed therapies have recently reached the clinic, albeit this has highlighted the increasing need to develop combinatorial therapies for...
Source: Cellular and Molecular Life Sciences : CMLS - April 6, 2021 Category: Cytology Authors: Rachel James Helena Chaytow Leire M Ledahawsky Thomas H Gillingwater Source Type: research

Biogenesis, physiological functions and potential applications of extracellular vesicles in substance use disorders
Cell Mol Life Sci. 2021 Apr 5. doi: 10.1007/s00018-021-03824-8. Online ahead of print.ABSTRACTSubstance use disorder (SUD) is a growing health problem that affects several millions of people worldwide, resulting in negative socioeconomic impacts and increased health care costs. Emerging evidence suggests that extracellular vesicles (EVs) play a crucial role in SUD pathogenesis. EVs, including exosomes and microvesicles, are membrane-encapsulated particles that are released into the extracellular space by most types of cells. EVs are important players in mediating cell-to-cell communication through transfer of cargo such as...
Source: Cellular and Molecular Life Sciences : CMLS - April 6, 2021 Category: Cytology Authors: Ernest T Chivero Raghubendra Singh Dagur Eric S Peeples Susmita Sil Ke Liao Rong Ma Liang Chen Channabasavaiah B Gurumurthy Shilpa Buch Guoku Hu Source Type: research

Revisiting the role of mitochondria in spinal muscular atrophy
Cell Mol Life Sci. 2021 Apr 5. doi: 10.1007/s00018-021-03819-5. Online ahead of print.ABSTRACTSpinal muscular atrophy (SMA) is an autosomal recessive motor neuron disease of variable clinical severity that is caused by mutations in the survival motor neuron 1 (SMN1) gene. Despite its name, SMN is a ubiquitous protein that functions within and outside the nervous system and has multiple cellular roles in transcription, translation, and proteostatic mechanisms. Encouragingly, several SMN-directed therapies have recently reached the clinic, albeit this has highlighted the increasing need to develop combinatorial therapies for...
Source: Cellular and Molecular Life Sciences : CMLS - April 6, 2021 Category: Cytology Authors: Rachel James Helena Chaytow Leire M Ledahawsky Thomas H Gillingwater Source Type: research

Biogenesis, physiological functions and potential applications of extracellular vesicles in substance use disorders
Cell Mol Life Sci. 2021 Apr 5. doi: 10.1007/s00018-021-03824-8. Online ahead of print.ABSTRACTSubstance use disorder (SUD) is a growing health problem that affects several millions of people worldwide, resulting in negative socioeconomic impacts and increased health care costs. Emerging evidence suggests that extracellular vesicles (EVs) play a crucial role in SUD pathogenesis. EVs, including exosomes and microvesicles, are membrane-encapsulated particles that are released into the extracellular space by most types of cells. EVs are important players in mediating cell-to-cell communication through transfer of cargo such as...
Source: Cellular and Molecular Life Sciences : CMLS - April 6, 2021 Category: Cytology Authors: Ernest T Chivero Raghubendra Singh Dagur Eric S Peeples Susmita Sil Ke Liao Rong Ma Liang Chen Channabasavaiah B Gurumurthy Shilpa Buch Guoku Hu Source Type: research

Cadherins in early neural development
Cell Mol Life Sci. 2021 Apr 1. doi: 10.1007/s00018-021-03815-9. Online ahead of print.ABSTRACTDuring early neural development, changes in signalling inform the expression of transcription factors that in turn instruct changes in cell identity. At the same time, switches in adhesion molecule expression result in cellular rearrangements that define the morphology of the emerging neural tube. It is becoming increasingly clear that these two processes influence each other; adhesion molecules do not simply operate downstream of or in parallel with changes in cell identity but rather actively feed into cell fate decisions. Why a...
Source: Cellular and Molecular Life Sciences : CMLS - April 2, 2021 Category: Cytology Authors: Karolina Punovuori Mattias Malaguti Sally Lowell Source Type: research

Cadherins in early neural development
Cell Mol Life Sci. 2021 Apr 1. doi: 10.1007/s00018-021-03815-9. Online ahead of print.ABSTRACTDuring early neural development, changes in signalling inform the expression of transcription factors that in turn instruct changes in cell identity. At the same time, switches in adhesion molecule expression result in cellular rearrangements that define the morphology of the emerging neural tube. It is becoming increasingly clear that these two processes influence each other; adhesion molecules do not simply operate downstream of or in parallel with changes in cell identity but rather actively feed into cell fate decisions. Why a...
Source: Cellular and Molecular Life Sciences : CMLS - April 2, 2021 Category: Cytology Authors: Karolina Punovuori Mattias Malaguti Sally Lowell Source Type: research

Cadherins in early neural development
Cell Mol Life Sci. 2021 Apr 1. doi: 10.1007/s00018-021-03815-9. Online ahead of print.ABSTRACTDuring early neural development, changes in signalling inform the expression of transcription factors that in turn instruct changes in cell identity. At the same time, switches in adhesion molecule expression result in cellular rearrangements that define the morphology of the emerging neural tube. It is becoming increasingly clear that these two processes influence each other; adhesion molecules do not simply operate downstream of or in parallel with changes in cell identity but rather actively feed into cell fate decisions. Why a...
Source: Cellular and Molecular Life Sciences : CMLS - April 2, 2021 Category: Cytology Authors: Karolina Punovuori Mattias Malaguti Sally Lowell Source Type: research

Cadherins in early neural development
Cell Mol Life Sci. 2021 Apr 1. doi: 10.1007/s00018-021-03815-9. Online ahead of print.ABSTRACTDuring early neural development, changes in signalling inform the expression of transcription factors that in turn instruct changes in cell identity. At the same time, switches in adhesion molecule expression result in cellular rearrangements that define the morphology of the emerging neural tube. It is becoming increasingly clear that these two processes influence each other; adhesion molecules do not simply operate downstream of or in parallel with changes in cell identity but rather actively feed into cell fate decisions. Why a...
Source: Cellular and Molecular Life Sciences : CMLS - April 2, 2021 Category: Cytology Authors: Karolina Punovuori Mattias Malaguti Sally Lowell Source Type: research

A lysosomal enigma CLN5 and its significance in understanding neuronal ceroid lipofuscinosis
Cell Mol Life Sci. 2021 Apr 1. doi: 10.1007/s00018-021-03813-x. Online ahead of print.ABSTRACTNeuronal Ceroid Lipofuscinosis (NCL), also known as Batten disease, is an incurable childhood brain disease. The thirteen forms of NCL are caused by mutations in thirteen CLN genes. Mutations in one CLN gene, CLN5, cause variant late-infantile NCL, with an age of onset between 4 and 7 years. The CLN5 protein is ubiquitously expressed in the majority of tissues studied and in the brain, CLN5 shows both neuronal and glial cell expression. Mutations in CLN5 are associated with the accumulation of autofluorescent storage material in l...
Source: Cellular and Molecular Life Sciences : CMLS - April 1, 2021 Category: Cytology Authors: I Basak H E Wicky K O McDonald J B Xu J E Palmer H L Best S Lefrancois S Y Lee L Schoderboeck S M Hughes Source Type: research

The role of heme oxygenase-1 in hematopoietic system and its microenvironment
Cell Mol Life Sci. 2021 Mar 31. doi: 10.1007/s00018-021-03803-z. Online ahead of print.ABSTRACTHematopoietic system transports all necessary nutrients to the whole organism and provides the immunological protection. Blood cells have high turnover, therefore, this system must be dynamically controlled and must have broad regeneration potential. In this review, we summarize how this complex system is regulated by the heme oxygenase-1 (HO-1)-an enzyme, which degrades heme to biliverdin, ferrous ion and carbon monoxide. First, we discuss how HO-1 influences hematopoietic stem cells (HSC) self-renewal, aging and differentiation...
Source: Cellular and Molecular Life Sciences : CMLS - March 31, 2021 Category: Cytology Authors: Agata Szade Krzysztof Szade Mahdi Mahdi Alicja J ózkowicz Source Type: research