SRF Expression in Excess Permits a Dual Contractile-Proliferative Phenotype of Airway Smooth Muscle
Am J Respir Cell Mol Biol. 2024 May 22. doi: 10.1165/rcmb.2024-0081OC. Online ahead of print.ABSTRACTThe transcription factors (TFs) myocardin (MyoCD) and ETS Like-1 protein (Elk-1) competitively bind to serum response factor (SRF) and control myogenic- and mitogenic-related gene expression in smooth muscle, respectively. Their functions are therefore mutually inhibitory, which result in a contractile versus proliferative phenotype dichotomy. Airway smooth muscle cell (ASMC) phenotype alterations occur in various inflammatory airway diseases, promoting pathological remodelling and contributing to airflow obstruction. We ch...
Source: Mol Biol Cell - May 22, 2024 Category: Molecular Biology Authors: Rui Sun Xingning Pan Erin Ward Rafael Intrevado Arina Morozan Anne-Marie Lauzon James G Martin Source Type: research

Differential reliance of CTD-nuclear envelope phosphatase 1 on its regulatory subunit in ER lipid synthesis and storage
Mol Biol Cell. 2024 May 22:mbcE23090382. doi: 10.1091/mbc.E23-09-0382. Online ahead of print.ABSTRACTLipin 1 is an ER enzyme that produces diacylglycerol, the lipid intermediate that feeds into the synthesis of glycerophospholipids for membrane expansion or triacylglycerol for storage into lipid droplets. CTD-Nuclear Envelope Phosphatase 1 (CTDNEP1) regulates lipin 1 to restrict ER membrane synthesis, but a role for CTDNEP1 in lipid storage in mammalian cells is not known. Here, we show that CTDNEP1 is reliant on its binding partner NEP1R1 for its stability and function in limiting ER expansion. CTDNEP1 contains an amphipa...
Source: Mol Biol Cell - May 22, 2024 Category: Molecular Biology Authors: Jake W Carrasquillo Rodr íguez Onyedikachi Uche Shujuan Gao Shoken Lee Michael V Airola Shirin Bahmanyar Source Type: research

Sur7 mediates a novel pathway for PI(4,5)P(2) regulation in C. albicans that promotes stress resistance and cell wall morphogenesis
Mol Biol Cell. 2024 May 22:mbcE23080324. doi: 10.1091/mbc.E23-08-0324. Online ahead of print.ABSTRACTThe human fungal pathogen Candida albicans can cause lethal systemic infections due to its ability to resist stress from the host and to undergo invasive hyphal growth. Previous studies showed that plasma membrane MCC/eisosome domains were important for virulence by promoting the ability of Sur7 to mediate normal cell wall morphogenesis and stress resistance. The sur7Δ mutant displayed abnormal clusters of PI4,5P2, suggesting that misregulation of this lipid underlies the sur7Δ phenotype. To test this, we increased PI4,5P...
Source: Mol Biol Cell - May 22, 2024 Category: Molecular Biology Authors: Carla E Lanze James B Konopka Source Type: research

Phase separation of SPIN1 through its IDR facilitates histone methylation readout and tumorigenesis
J Mol Cell Biol. 2024 May 22:mjae024. doi: 10.1093/jmcb/mjae024. Online ahead of print.ABSTRACTSpindlin1 (SPIN1) is a unique multivalent histone modification reader that plays a role in ribosomal RNA transcription, chromosome segregation, and tumorigenesis. However, the function of the extended N-terminal region of SPIN1 has remained unclear. Here, we discovered that SPIN1 can form phase-separated and liquid-like condensates both in vitro and in vivo through its N-terminal intrinsically disordered region (IDR). The phase separation of SPIN1 recruits the histone methyltransferase MLL1 to the same condensates and enriches th...
Source: Mol Biol Cell - May 22, 2024 Category: Molecular Biology Authors: Yukun Wang Yuhan Chen Mengyao Li Jiayue Wang Yuhan Jiang Rong Xie Yifeng Zhang Zhihua Li Zhenzhen Yan Chen Wu Source Type: research

Electrospinning Approach for Preparing Nanostructured Scaffolds for Stem Cell Seeding and/or Implantation in Neurotrauma
Methods Mol Biol. 2024 May 23. doi: 10.1007/7651_2024_547. Online ahead of print.ABSTRACTPreparation of highly porous biocompatible and bioresorbable nerve conduit or scaffold by electrospinning based on synthetic polycaprolactone with a molecular weight of 80 kDa (PCL 80 kDa) has significance in the context of regenerative medicine with special emphasis on their application in neurotrauma. PCL conduits/scaffolds serving as a support structure for seeded stem cells show promising regenerative potential to promote functional recovery and tissue regeneration in models of neurotrauma. Here we describe a standard protocol for ...
Source: Mol Biol Cell - May 22, 2024 Category: Molecular Biology Authors: Eldar F Davletshin Albert A Rizvanov Yana O Mukhamedshina Source Type: research

Telocytes: Detection, Visualization, Tissue Dissociation, and Tamoxifen-Induction of Transgenic Mice
Methods Mol Biol. 2024 May 23. doi: 10.1007/7651_2024_549. Online ahead of print.ABSTRACTTelocytes, distinctive interstitial cells, have recently emerged as crucial components of the stem-cell niche in the intestine. Notably, telocytes are distinguished by their extremely long cellular protrusions extending hundreds of microns from the cell body, forming an interconnected network along the intestinal crypt villus axis. Due to these unique cellular characteristics, there is a need for tailored working protocols to effectively characterize and target telocytes. Here, we outline advanced and progressive protocols for tissue f...
Source: Mol Biol Cell - May 22, 2024 Category: Molecular Biology Authors: Marco Canella Michal Shoshkes-Carmel Source Type: research

SLAM-Drop-seq reveals mRNA kinetic rates throughout the cell cycle
Mol Syst Biol. 2023 Oct;19(10):1-23. doi: 10.15252/msb.202211427. Epub 2023 Aug 28.NO ABSTRACTPMID:38778223 | DOI:10.15252/msb.202211427 (Source: Mol Biol Cell)
Source: Mol Biol Cell - May 22, 2024 Category: Molecular Biology Authors: Haiyue Liu Roberto Arsi è Daniel Schwabe Marcel Schilling Igor Minia Jonathan Alles Anastasiya Boltengagen Christine Kocks Martin Falcke Nir Friedman Markus Landthaler Nikolaus Rajewsky Source Type: research

SR proteins in cancer: function, regulation, and small inhibitor
Cell Mol Biol Lett. 2024 May 22;29(1):78. doi: 10.1186/s11658-024-00594-6.ABSTRACTAlternative splicing of pre-mRNAs is a fundamental step in RNA processing required for gene expression in most metazoans. Serine and arginine-rich proteins (SR proteins) comprise a family of multifunctional proteins that contain an RNA recognition motif (RRM) and the ultra-conserved arginine/serine-rich (RS) domain, and play an important role in precise alternative splicing. Increasing research supports SR proteins as also functioning in other RNA-processing-related mechanisms, such as polyadenylation, degradation, and translation. In additio...
Source: Mol Biol Cell - May 22, 2024 Category: Molecular Biology Authors: Mingrong Bei Jianzhen Xu Source Type: research

Increased ANKRD1 Levels in Early Senescence Mediated by RBMS1-Elicited < em > ANKRD1 < /em > mRNA Stabilization
Mol Cell Biol. 2024 May 20:1-15. doi: 10.1080/10985549.2024.2350540. Online ahead of print.ABSTRACTCellular senescence is a dynamic biological process triggered by sublethal cell damage and driven by specific changes in gene expression programs. We recently identified ANKRD1 (ankyrin repeat domain 1) as a protein strongly elevated after triggering senescence in fibroblasts. Here, we set out to investigate the mechanisms driving the elevated production of ANKRD1 in the early stages of senescence. Our results indicated that the rise in ANKRD1 levels after triggering senescence using etoposide (Eto) was the result of moderate...
Source: Mol Biol Cell - May 21, 2024 Category: Molecular Biology Authors: Chang Hoon Shin Martina Rossi Carlos Anerillas Jennifer L Martindale Xiaoling Yang Eunbyul Ji Apala Pal Rachel Munk Jen-Hao Yang Dimitrios Tsitsipatis Krystyna Mazan-Mamczarz Kotb Abdelmohsen Myriam Gorospe Source Type: research

CSPP1 preserves quiescent microtubule functions by dual-end capping
J Mol Cell Biol. 2024 May 21:mjae022. doi: 10.1093/jmcb/mjae022. Online ahead of print.NO ABSTRACTPMID:38772741 | DOI:10.1093/jmcb/mjae022 (Source: Mol Biol Cell)
Source: Mol Biol Cell - May 21, 2024 Category: Molecular Biology Authors: Marina Mapelli Source Type: research

Splicing regulation through biomolecular condensates and membraneless organelles
Nat Rev Mol Cell Biol. 2024 May 21. doi: 10.1038/s41580-024-00739-7. Online ahead of print.ABSTRACTBiomolecular condensates, sometimes also known as membraneless organelles (MLOs), can form through weak multivalent intermolecular interactions of proteins and nucleic acids, a process often associated with liquid-liquid phase separation. Biomolecular condensates are emerging as sites and regulatory platforms of vital cellular functions, including transcription and RNA processing. In the first part of this Review, we comprehensively discuss how alternative splicing regulates the formation and properties of condensates, and co...
Source: Mol Biol Cell - May 21, 2024 Category: Molecular Biology Authors: Jimena Giudice Hao Jiang Source Type: research

eIF4A1 enhances LARP1-mediated translational repression during mTORC1 inhibition
Nat Struct Mol Biol. 2024 May 21. doi: 10.1038/s41594-024-01321-7. Online ahead of print.ABSTRACTEukaryotic translation initiation factor (eIF)4A-a DEAD-box RNA-binding protein-plays an essential role in translation initiation. Recent reports have suggested helicase-dependent and helicase-independent functions for eIF4A, but the multifaceted roles of eIF4A have not been fully explored. Here we show that eIF4A1 enhances translational repression during the inhibition of mechanistic target of rapamycin complex 1 (mTORC1), an essential kinase complex controlling cell proliferation. RNA pulldown followed by sequencing revealed ...
Source: Mol Biol Cell - May 21, 2024 Category: Molecular Biology Authors: Yuichi Shichino Tomokazu Yamaguchi Kazuhiro Kashiwagi Mari Mito Mari Takahashi Takuhiro Ito Nicholas T Ingolia Keiji Kuba Shintaro Iwasaki Source Type: research

Increased ANKRD1 Levels in Early Senescence Mediated by RBMS1-Elicited < em > ANKRD1 < /em > mRNA Stabilization
Mol Cell Biol. 2024 May 20:1-15. doi: 10.1080/10985549.2024.2350540. Online ahead of print.ABSTRACTCellular senescence is a dynamic biological process triggered by sublethal cell damage and driven by specific changes in gene expression programs. We recently identified ANKRD1 (ankyrin repeat domain 1) as a protein strongly elevated after triggering senescence in fibroblasts. Here, we set out to investigate the mechanisms driving the elevated production of ANKRD1 in the early stages of senescence. Our results indicated that the rise in ANKRD1 levels after triggering senescence using etoposide (Eto) was the result of moderate...
Source: Mol Biol Cell - May 21, 2024 Category: Molecular Biology Authors: Chang Hoon Shin Martina Rossi Carlos Anerillas Jennifer L Martindale Xiaoling Yang Eunbyul Ji Apala Pal Rachel Munk Jen-Hao Yang Dimitrios Tsitsipatis Krystyna Mazan-Mamczarz Kotb Abdelmohsen Myriam Gorospe Source Type: research

Biophysical characterization and insights into the oligomeric nature of CD2-associated protein
CONCLUSION: We successfully expressed full-length human CD2AP in a heterologous system, wherein the secondary structure of CD2AP is predominantly disordered. CD2AP can form higher-order oligomers, and the significance of these oligomers and the impact of mutations in the context of size-selective permeability of SD needs further investigation.PMID:38765876 | PMC:PMC11101965 | DOI:10.62347/UVSH8436 (Source: Mol Biol Cell)
Source: Mol Biol Cell - May 20, 2024 Category: Molecular Biology Authors: Abrar H Qadri Jyotsana Prajapati Iqball Faheem Utsa Bhattacharjee Hari Krishnan Padmanaban Sandeep Kn Mulukala Anil K Pasupulati Source Type: research

TCF12 Transcriptionally Activates SPHK1 to Induce Osteosarcoma Angiogenesis by Promoting the S1P/S1PR4/STAT3 Axis
In this study, we demonstrated increased expression of TCF12 in osteosarcoma tissues and cell lines. High TCF12 expression was associated with metastasis and poor survival rate of osteosarcoma patients. Knockdown of TCF12 reduced the proliferation, migration, and invasion of osteosarcoma cells. TCF12 was found to bind to the promoter region of sphingosine kinase 1 (SPHK1) to induce transcriptional activation of SPHK1 expression and enhance the secretion of sphingosine-1-phosphate (S1P), which eventually resulted in the malignant phenotypes of osteosarcoma cells. In addition, S1P secreted by osteosarcoma cells promoted the ...
Source: Mol Biol Cell - May 20, 2024 Category: Molecular Biology Authors: Wo Li Jitong Liu Ting Cai Xia Hu Source Type: research