Calcium signaling defects underlying salivary gland dysfunction
Publication date: Available online 10 July 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Cell ResearchAuthor(s): Indu AmbudkarAbstractSalivary glands secrete saliva, a mixture of proteins and fluids, which plays an extremely important role in the maintenance of oral health. Loss of salivary secretion causes a dry mouth condition, xerostomia, which has numerous deleterious consequences including opportunistic infections within the oral cavity, difficulties in eating and swallowing food, and problems with speech. Saliva secretion is regulated by stimulation of specific signaling mechanisms within the acinar cel...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - July 11, 2018 Category: Molecular Biology Source Type: research

Sphingolipid-mediated calcium signaling and its pathological effects
Publication date: Available online 26 April 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Cell ResearchAuthor(s): Ilari Pulli, Muhammad Yasir Asghar, Kati Kemppainen, Kid TörnquistAbstractMetabolites of sphingomyelin, as well as calcium ion fluxes, have a profound role in cellular signaling in almost all cell types. In addition, metabolites of sphingomyelin often modulate calcium signaling, either directly or indirectly. This is an interesting aspect on how lipids may wield their physiological role, as calcium is probably one of the most versatile signaling molecules in the cell, and as modulation of cal...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - July 11, 2018 Category: Molecular Biology Source Type: research

Two-pore channels and disease
Publication date: Available online 7 May 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Cell ResearchAuthor(s): Sandip Patel, Bethan S. KilpatrickAbstractTwo-pore channels (TPCs) are Ca2+-permeable endo-lysosomal ion channels subject to multi-modal regulation. They mediate their physiological effects through releasing Ca2+ from acidic organelles in response to cues such as the second messenger, NAADP. Here, we review emerging evidence linking TPCs to disease. We discuss how perturbing both local and global Ca2+ changes mediated by TPCs through chemical and/or molecular manipulations can induce or reverse disea...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - July 11, 2018 Category: Molecular Biology Source Type: research

The role of Ca2+ in oocyte activation during In Vitro fertilization: Insights into potential therapies for rescuing failed fertilization
Publication date: Available online 8 May 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Cell ResearchAuthor(s): Karl SwannAbstractAt fertilization the mature mammalian oocyte is activated to begin development by a sperm-induced series of increases in the cytosolic free Ca2+ concentration. These so called Ca2+ oscillations, or repetitive Ca2+ spikes, are also seen after intracytoplasmic sperm injection (ICSI) and are primarily triggered by a sperm protein called phospholipase Czeta (PLCζ). Whilst ICSI is generally an effective way to fertilizing human oocytes, there are cases where oocyte activation fails ...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - July 11, 2018 Category: Molecular Biology Source Type: research

NCS-1 is a regulator of calcium signaling in health and disease
The objective of this article is to summarize the current body of evidence describing NCS-1 and its interactions on a molecular and cellular scale, as well as describing macroscopic implications in physiology and medicine. Particular attention is paid to the role of NCS-1 in development and prevention of chemotherapy induced peripheral neuropathy (CIPN). (Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research)
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - July 11, 2018 Category: Molecular Biology Source Type: research

Altered Ca2+ signaling in enamelopathies
Publication date: Available online 9 May 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Cell ResearchAuthor(s): Miriam Eckstein, Francisco J. Aulestia, Meerim K. Nurbaeva, Rodrigo S. LacruzAbstractBiomineralization requires the controlled movement of ions across cell barriers to reach the sites of crystal growth. Mineral precipitation occurs in aqueous phases as fluids become supersaturated with specific ionic compositions. In the biological world, biomineralization is dominated by the presence of calcium (Ca2+) in crystal lattices. Ca2+ channels are intrinsic modulators of this process, facilitating the avail...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - July 11, 2018 Category: Molecular Biology Source Type: research

Ca2+ signaling and spinocerebellar ataxia
Publication date: Available online 16 May 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Cell ResearchAuthor(s): Chihiro Hisatsune, Kozo Hamada, Katsuhiko MikoshibaAbstractSpinocerebellar ataxia (SCA) is a neural disorder, which is caused by degenerative changes in the cerebellum. SCA is primarily characterized by gait ataxia, and additional clinical features include nystagmus, dysarthria, tremors and cerebellar atrophy. Forty-four hereditary SCAs have been identified to date, along with>35 SCA-associated genes. Despite the great diversity and distinct functionalities of the SCA-related genes, accumulating ...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - July 11, 2018 Category: Molecular Biology Source Type: research

Regulation of bile secretion by calcium signaling in health and disease
Publication date: Available online 19 May 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Cell ResearchAuthor(s): David C. Trampert, Michael H. NathansonAbstractCalcium (Ca2+) signaling controls secretion in many types of cells and tissues. In the liver, Ca2+ regulates secretion in both hepatocytes, which are responsible for primary formation of bile, and cholangiocytes, which line the biliary tree and further condition the bile before it is secreted. Cholestatic liver diseases, which are characterized by impaired bile secretion, may result from impaired Ca2+ signaling mechanisms in either hepatocytes or cholan...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - July 11, 2018 Category: Molecular Biology Source Type: research

Calcium signaling and the therapeutic targeting of cancer cells
Publication date: Available online 26 May 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Cell ResearchAuthor(s): Alice H.L. Bong, Gregory R. MonteithAbstractThe calcium signal is implicated in a variety of processes important in tumor progression (e.g. proliferation and invasiveness). The calcium signal has also been shown to be important in other processes important in cancer progression including the development of resistance to current cancer therapies. In this review, we discuss how Ca2+ channels, pumps and exchangers may be drug targets in some cancer types. We consider what factors should be taken into a...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - July 11, 2018 Category: Molecular Biology Source Type: research

Corrigendum to “Tensin1 positively regulates RhoA activity through its interaction with DLC1” [Biochimica et Biophysica Acta 1853/12 (2015) 3258–3265]
Publication date: Available online 2 June 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Cell ResearchAuthor(s): Yi-Ping Shih, Peng Sun, Aifeng Wang, Su Hao Lo (Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research)
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - July 11, 2018 Category: Molecular Biology Source Type: research

Pathophysiological consequences of isoform-specific IP3 receptor mutations
Publication date: Available online 12 June 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Cell ResearchAuthor(s): Martijn Kerkhofs, Bruno Seitaj, Hristina Ivanova, Giovanni Monaco, Geert Bultynck, Jan B. ParysAbstractCa2+ signaling governs a diverse range of cellular processes and, as such, is subject to tight regulation. A main component of the complex intracellular Ca2+-signaling network is the inositol 1,4,5-trisphosphate (IP3) receptor (IP3R), a tetrameric channel that mediates Ca2+ release from the endoplasmic reticulum (ER) in response to IP3. IP3R function is controlled by a myriad of factors, such as C...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - July 11, 2018 Category: Molecular Biology Source Type: research

Glutamine-dependent lysosome homeostatic changes induced by starvation and lysosome inhibition
Publication date: Available online 30 June 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Cell ResearchAuthor(s): Alexa R. Wilden, Joshua A. Molina, Melissa Feuerborn, Daniel Boyle, Stella Y. LeeAbstractLysosomes are a major organelle for degrading macromolecules. When deprived of nutrients, cells activate the autophagy and lysosome biogenesis pathways to recycle cytoplasmic materials and to increase lysosomal degradation capacity for survival, respectively. We have identified a condition in which cells accumulated enlarged lysosomes upon starvation and lysosome inhibition. Selective autophagy and inhibition o...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - July 11, 2018 Category: Molecular Biology Source Type: research

Lysosomal N-acetyltransferase interacts with ALIX and is detected in extracellular vesicles
In this study, HGSNAT activity was detected in extracellular vesicles isolated from both human urine and culture medium conditioned with HEK 293T cells. We also demonstrate that HGSNAT co-immunoprecipitates with antibodies to ALIX, which is associated with the endosomal sorting complexes required for transport (ESCRT) proteins, and is implicated in the targeting of proteins to intraluminal vesicles of multivesicular bodies, the origin of exosomes. Furthermore, mutation of a putative LYPXnL-based binding site within HGSNAT for the V-domain of ALIX ablated association of HGSNAT with ALIX, post-translational maturation, and t...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - July 11, 2018 Category: Molecular Biology Source Type: research

Modeling endophilin-mediated Aβ disposal in glioma cells
Publication date: Available online 4 July 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Cell ResearchAuthor(s): Bing Sun, Ping Fan, Meijian Liao, Yaou ZhangAbstractAutophagy dysregulation has emerged in age-related neurological diseases (Ulland et al.; Matheoud et al.; Ashkenazi et al. [[1], [2], [3]]). Alzheimer Disease (AD), the most common progressive neurodegenerative disorder, is characterized by the accumulation of amyloid-β (Aβ) plaques caused by aberrant Aβ metabolism (Qiang et al.; Sevigny et al.; Ittner et al. [[4], [5], [6]]). Glia constitute the brain immune system and ingest extrac...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - July 11, 2018 Category: Molecular Biology Source Type: research

The role of protein tyrosine phosphatases in prostate cancer biology
Publication date: Available online 4 July 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Cell ResearchAuthor(s): Caroline E. Nunes-Xavier, Janire Mingo, José I. López, Rafael PulidoAbstractProstate cancer (PCa) is the most frequent malignancy in the male population of Western countries. Although earlier detection and more active surveillance have improved survival, it is still a challenge how to treat advanced cases. Since androgen receptor (AR) and AR-related signaling pathways are fundamental in the growth of normal and neoplastic prostate cells, targeting androgen synthesis or AR activity cons...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - July 11, 2018 Category: Molecular Biology Source Type: research

Structural bases of the assembly, recognition and disassembly of linear ubiquitin chain
Publication date: Available online 5 July 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Cell ResearchAuthor(s): Jianping Liu, Lifeng PanAbstractLinear ubiquitin chain is a latest discovered type of poly-ubiquitin chain that is broadly involved in innate immune and inflammatory pathways. Dysfunctions in its assembly, recognition or disassembly are intimately related with numerous immunodeficiency or autoimmune diseases. Our understanding of the molecular mechanism for linear ubiquitin chain formation, recognition and disassembly has being significantly evolved in recent years, with particular contribution from...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - July 11, 2018 Category: Molecular Biology Source Type: research

Editorial Board
Publication date: August 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Volume 1865, Issue 8Author(s): (Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research)
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - July 11, 2018 Category: Molecular Biology Source Type: research

IKK1/2 protect human cells from TNF-mediated RIPK1-dependent apoptosis in an NF-κB-independent manner
Publication date: August 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Volume 1865, Issue 8Author(s): Carsten Slotta, Jonathan Storm, Nina Pfisterer, Elena Henkel, Svenja Kleinwächter, Maren Pieper, Lucia M. Ruiz-Perera, Johannes F.W. Greiner, Barbara Kaltschmidt, Christian KaltschmidtAbstractTNF signaling is directly linked to cancer development and progression. A broad range of tumor cells is able to evade cell death induced by TNF impairing the potential anti-cancer value of TNF in therapy. Although sensitizing cells to TNF-induced death therefore has great clinical implications, detail...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - July 11, 2018 Category: Molecular Biology Source Type: research

MDM2 controls NRF2 antioxidant activity in prevention of diabetic kidney disease
Publication date: August 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Volume 1865, Issue 8Author(s): Weiying Guo, Dan Tian, Ye Jia, Wenlin Huang, Mengnan Jiang, Junnan Wang, Weixia Sun, Hao WuAbstractOxidative stress and P53 contribute to the pathogenesis of diabetic kidney disease (DKD). Nuclear factor erythroid 2-related factor 2 (NRF2) is a master regulator of cellular antioxidant defense system, is negatively regulated by P53 and prevents DKD. Recent findings revealed an important role of mouse double minute 2 (MDM2) in protection against DKD. However, the mechanism remained unclear. We hy...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - July 11, 2018 Category: Molecular Biology Source Type: research

The origin of GSKIP, a multifaceted regulatory factor in the mammalian Wnt pathway
In this study, bioinformatics and experimental explorations re-analyzing GSKIP's biofunctions suggest that the evolutionarily conserved Domain of Unknown Function (DUF727) is an ancestral prototype of GSKIP in prokaryotes, and acquired the C-terminal GSK3β binding site (tail) in invertebrates except for Saccharomyces spp., after which the N-terminal PKA-RII binding region (head) evolved in vertebrates. These two regions mutually influence each other and modulate GSKIP binding to GSK3β in yeast two-hybrid assays and co-immunoprecipitation. Molecular modeling showed that mammalian GSKIP could form a dimer through t...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - July 11, 2018 Category: Molecular Biology Source Type: research

The nonreceptor tyrosine kinase c-Abl phosphorylates Runx1 and regulates Runx1-mediated megakaryocyte maturation
In this study, we showed that c-Abl, but not Arg tyrosine kinase, associated with Runx1 both in cultured cells and in vitro. c-Abl-mediated tyrosine phosphorylation in the Runx1 transcription inhibition domain negatively regulated the transcriptional activity of Runx1 and inhibited Runx1-mediated MK maturation. Consistent with these findings, increased numbers of MKs were detected in the spleens and bone marrow of abl gene conditional knockout mice. Our findings demonstrate an important role of c-Abl kinase in Runx1-mediated MK maturation and platelet formation and provide a potential mechanism of Abl kinase-regulated hema...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - July 11, 2018 Category: Molecular Biology Source Type: research

Distinct apoptotic blocks mediate resistance to panHER inhibitors in HER2+ breast cancer cells
Publication date: August 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Volume 1865, Issue 8Author(s): Bahriye Karakas, Yeliz Ozmay, Huveyda Basaga, Ozgur Gul, Ozgur KutukAbstractDespite the development of novel targeted therapies, de novo or acquired chemoresistance remains a significant factor for treatment failure in breast cancer therapeutics. Neratinib and dacomitinib are irreversible panHER inhibitors, which block their autophosphorylation and downstream signaling. Moreover, neratinib and dacomitinib have been shown to activate cell death in HER2-overexpressing cell lines. Here we showed t...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - July 11, 2018 Category: Molecular Biology Source Type: research

E3 ubiquitin ligase HECW2 targets PCNA and lamin B1
Publication date: August 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Volume 1865, Issue 8Author(s): Vidhya Krishnamoorthy, Richa Khanna, Veena K. ParnaikAbstractLamins constitute the major architectural proteins of the nuclear lamina that help in maintaining nuclear organization. Mutations in lamins are associated with diverse degenerative diseases, collectively termed laminopathies. HECW2, a HECT-type E3 ubiquitin ligase, is transcriptionally upregulated in HeLa cells expressing Emery-Dreifuss muscular dystrophy-causing-lamin A mutants. However, the role of HECW2 upregulation in mediating do...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - July 11, 2018 Category: Molecular Biology Source Type: research

Autophagy regulates apoptosis by targeting NOXA for degradation
Publication date: August 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Volume 1865, Issue 8Author(s): Jingchao Wang, Danrui Cui, Shanshan Gu, Xiaoyu Chen, Yanli Bi, Xiufang Xiong, Yongchao ZhaoAbstractApoptosis and autophagy mutually regulate various cellular physiological and pathological processes. The crosstalk between autophagy and apoptosis is multifaceted and complicated. Elucidating the molecular mechanism of their crosstalk will advance the therapeutic applications of autophagy for treating cancer and other diseases. NOXA, a BH3-only member of the BCL-2 family, was reported to induce ap...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - July 11, 2018 Category: Molecular Biology Source Type: research

Contribution of the residue at position 4 within classical nuclear localization signals to modulating interaction with importins and nuclear targeting
Publication date: August 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Volume 1865, Issue 8Author(s): Kate M. Smith, Veronica Di Antonio, Luca Bellucci, David R. Thomas, Fabiana Caporuscio, Francesco Ciccarese, Hanieh Ghassabian, Kylie M. Wagstaff, Jade K. Forwood, David A. Jans, Giorgio Palù, Gualtiero AlvisiAbstractNuclear import involves the recognition by importin (IMP) superfamily members of nuclear localization signals (NLSs) within protein cargoes destined for the nucleus, the best understood being recognition of classical NLSs (cNLSs) by the IMPα/β1 heterodimer. Althou...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - July 11, 2018 Category: Molecular Biology Source Type: research

Circ-8073 regulates CEP55 by sponging miR-449a to promote caprine endometrial epithelial cells proliferation via the PI3K/AKT/mTOR pathway
Publication date: August 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Volume 1865, Issue 8Author(s): Xiaorui Liu, Lei Zhang, Yuexia Liu, Jiuzeng Cui, Sicheng Che, Xiaopeng An, Yuxuan Song, Binyun CaoAbstractCircular RNAs (circRNAs) are a large class of endogenous non-coding RNAs that function as regulators in various cells and tissues. Here, the function and mechanism of circRNA8073 (Circ-8073) on endometrial epithelial cells (EECs) and the development of endometrial receptivity were investigated in dairy goats. Circ-8073 could bind to and inhibit miR-449a activity. Circ-8073 binding to the ta...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - July 11, 2018 Category: Molecular Biology Source Type: research

A novel signal sequence negative multimeric glycosomal protein required for cell cycle progression of Leishmania donovani parasites
Publication date: August 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Volume 1865, Issue 8Author(s): Kavita Ahuja, Mirza Adil Beg, Ruby Sharma, Ajay Saxena, Nilofer Naqvi, Niti Puri, Pradeep Kumar Rai, Ashok Chaudhury, Robert Duncan, Poonam Salotra, Hira Nakhasi, Angamuthu SelvapandiyanAbstractExpression of the intracellular form amastigote specific genes in the Leishmania donovani parasite plays a major role in parasite replication in the macrophage. In the current work, we have characterized a novel hypothetical gene, Ld30b that is specifically transcribed in the intracellular stage of the p...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - July 11, 2018 Category: Molecular Biology Source Type: research

Dynamic L-type CaV1.2 channel trafficking facilitates CaV1.2 clustering and cooperative gating
Publication date: September 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Volume 1865, Issue 9Author(s): Debapriya Ghosh, Madeline Nieves-Cintrón, Sendoa Tajada, Ingrid Brust-Mascher, Mary C. Horne, Johannes W. Hell, Rose E. Dixon, Luis F. Santana, Manuel F. NavedoAbstractL-type CaV1.2 channels are key regulators of gene expression, cell excitability and muscle contraction. CaV1.2 channels organize in clusters throughout the plasma membrane. This channel organization has been suggested to contribute to the concerted activation of adjacent CaV1.2 channels (e.g. cooperative gating). Here, ...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - July 11, 2018 Category: Molecular Biology Source Type: research

mTORC1 pathway in DNA damage response
Publication date: September 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Volume 1865, Issue 9Author(s): Yinxing Ma, Yegor Vassetzky, Svetlana DokudovskayaAbstractLiving organisms have evolved various mechanisms to control their metabolism and response to various stresses, allowing them to survive and grow in different environments. In eukaryotes, the highly conserved mechanistic target of rapamycin (mTOR) signaling pathway integrates both intracellular and extracellular signals and serves as a central regulator of cellular metabolism, proliferation and survival. A growing body of evidence indi...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - July 11, 2018 Category: Molecular Biology Source Type: research

SRSF5 functions as a novel oncogenic splicing factor and is upregulated by oncogene SRSF3 in oral squamous cell carcinoma
Publication date: September 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Volume 1865, Issue 9Author(s): Sisi Yang, Rong Jia, Zhuan BianAbstractAlternative splicing of precursor messenger RNA has been increasingly associated with tumorigenesis. The serine/arginine-rich protein (SR) family plays key roles in the regulation of pre-mRNA alternative splicing. Increasing evidence has demonstrated that the SR protein family is involved in tumorigenesis. However, the functions and mechanisms of SR proteins in tumourigenesis remain largely unknown. In the present study, we discovered that serine/argini...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - July 11, 2018 Category: Molecular Biology Source Type: research

c-Abl phosphorylation of Yin Yang 1's conserved tyrosine 254 in the spacer region modulates its transcriptional activity
In conclusion, we demonstrate the novel role of c-Abl kinase in regulation of YY1's transcriptional activity, linking YY1 regulation with c-Abl tyrosine kinase signaling pathways.Graphical abstract (Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research)
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - July 11, 2018 Category: Molecular Biology Source Type: research

Molecular mechanisms involved in epidermal growth factor receptor-mediated inhibition of dopamine D3 receptor signaling
This study identified the molecular mechanisms involved in the EGFR-mediated regulation of the functions of D3R, which can be extended to the crosstalk between other RTKs and GPCRs.Graphical abstract (Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research)
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - July 11, 2018 Category: Molecular Biology Source Type: research

Lethal (2) giant larvae regulates pleural mesothelial cell polarity in pleural fibrosis
In this study, we observed that PMC polarity was lost in fibrotic pleura. Next we found increased Lethal (2) giant larvae (Lgl) bound with aPKC and PAR-6B competing against PAR-3A in PAR complex, which led to cell polarity loss. Then we demonstrated that Lgl1 siRNA prevented cell polarity loss in PMCs, and Lgl1 conditional knockout (ER-Cre+/−Lgl1flox/flox) attenuated pleural fibrosis in a mouse model. Our data indicated that Lgl1 regulates cell polarity of PMCs, inhibition of Lgl1 and maintenance of cell polarity in PMCs could be a potential therapeutic treatment approach for pleural fibrosis. (Source: Biochimica et ...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - July 11, 2018 Category: Molecular Biology Source Type: research

Prazosin induced lysosomal tubulation interferes with cytokinesis and the endocytic sorting of the tumour antigen CD98hc
Publication date: September 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Volume 1865, Issue 9Author(s): Robert Fuchs, Anika Stracke, Viktoria Holzmann, Gerfried Luschin-Ebengreuth, Nathalie Meier-Allard, Nadine Ebner, Teresa Maria Lassacher, Markus Absenger-Novak, Eleonore Fröhlich, Matthias Schittmayer, Sara Cano Crespo, Manuel Palacin, Beate Rinner, Ruth Birner-GruenbergerAbstractThe quinazoline based drug prazosin (PRZ) is a potent inducer of apoptosis in human cancer cells. We recently reported that PRZ enters cells via endocytosis and induces tubulation of the endolysosomal system. I...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - July 11, 2018 Category: Molecular Biology Source Type: research

Novel short isoforms of adenylyl cyclase as negative regulators of cAMP production
Publication date: September 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Volume 1865, Issue 9Author(s): Benjamin Vallin, Yohan Legueux-Cajgfinger, Nathalie Clément, Martine Glorian, Laurent Duca, Pierre Vincent, Isabelle Limon, Régis BlaiseAbstractHere, we cloned a new family of four adenylyl cyclase (AC) splice variants from interleukin-1β (IL-1β)-transdifferentiated vascular smooth muscle cells (VSMCs) encoding short forms of AC8 that we have named “AC8E-H”. Using biosensor imaging and biochemical approaches, we showed that AC8E-H isoforms have no cyclase ...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - July 11, 2018 Category: Molecular Biology Source Type: research

TGF-β and BMP signals regulate insect diapause through Smad1-POU-TFAM pathway
In this study, we find that TGF-β superfamily signaling regulates Helicoverpa armigera diapause via a novel mechanism. Both TGF-β and BMP signals are weaker in the brains of diapause-destined pupae than in nondiapause-destined pupae, and the levels of p-Smad1, POU, TFAM, and mitochondrial activity are decreased in diapause pupae. Development in nondiapause pupae is delayed by an injection of TGF-β or BMP receptor inhibitors. Both TGF-β and BMP signals can activate a common target, Smad1. ChIP and EMSA assays indicate that Smad1 can bind to the POU promoter to regulate its expression. POU can improve the...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - July 11, 2018 Category: Molecular Biology Source Type: research

Conserved functions of Arabidopsis mitochondrial late-acting maturation factors in the trafficking of iron‑sulfur clusters
In this study, we expressed the factors belonging to NFU, BOLA, SUFA/ISCA and IBA57 families in the respective yeast mutant strains. Expression of the Arabidopsis mitochondrial orthologs was usually sufficient to rescue the growth defects observed on specific media and/or to restore the abundance or activity of the defective Fe-S or lipoic acid-dependent enzymes. These data demonstrate that the plant mitochondrial counterparts, including duplicated isoforms, likely retained their ancestral functions. In contrast, the SUFA1 and IBA57.2 plastidial isoforms cannot rescue the lysine and glutamate auxotrophies of the respective...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - July 11, 2018 Category: Molecular Biology Source Type: research

NLRX1 resides in mitochondrial RNA granules and regulates mitochondrial RNA processing and bioenergetic adaptation
Publication date: September 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Volume 1865, Issue 9Author(s): Kritarth Singh, Lakshmi Sripada, Anastasia Lipatova, Milton Roy, Paresh Prajapati, Dhruv Gohel, Khyati Bhatelia, Peter M. Chumakov, Rajesh SinghAbstractThe role of mitochondria is emerging in regulation of innate immunity, inflammation and cell death beyond its primary role in energy metabolism. Mitochondria act as molecular platform for immune adaptor protein complexes, which participate in innate immune signaling. The mitochondrial localized immune adaptors are widely expressed in non-immu...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - July 11, 2018 Category: Molecular Biology Source Type: research

Hepatic Rac1 GTPase contributes to liver-mediated basal immune homeostasis and LPS-induced endotoxemia
ConclusionsRac1-dependent mechanisms in hepatocytes and non-hepatocytes contribute to the maintenance of liver immune homeostasis under basal situation and following LPS-induced endotoxemia. Disturbed Rac1-regulated hepatocyte functions may promote liver damage under pathophysiological situation involving inflammatory stress. (Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research)
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - July 11, 2018 Category: Molecular Biology Source Type: research

The intracellular domain of the leptin receptor prevents mitochondrial depolarization and mitophagy
This study demonstrates that regulated intramembrane proteolysis (RIP) releases the LR intracellular domain (LR ICD), which translocates to the mitochondria where it binds to SOCS6. This LR ICD-SOCS6 interaction stabilizes both proteins on the mitochondrial outer membrane and requires a functional BC box in SOCS6 for mitochondrial association and a central motif in the LR ICD for SOCS6 binding. The LR ICD prevents CCCP-induced mitochondrial depolarization and mitophagy as shown by lowered Parkin translocation and p62 accumulation. Strict regulation of mitochondrial dynamics in the hypothalamus is known to be essential for ...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - July 11, 2018 Category: Molecular Biology Source Type: research

Inhibition of the AnxA1/FPR1 autocrine axis reduces MDA-MB-231 breast cancer cell growth and aggressiveness in vitro and in vivo
Publication date: September 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Volume 1865, Issue 9Author(s): Lara Vecchi, Mariana Alves Pereira Zóia, Tiago Goss Santos, Adriano de Oliveira Beserra, Cristiano Manuel Colaço Ramos, Bruna França Matias Colombo, Yara Cristina Paiva Maia, Victor Piana de Andrade, Sara Teixeira Soares Mota, Thaise Gonçalves de Araújo, Fernanda Van Petten de Vasconcelos Azevedo, Fernando Augusto Soares, Sonia Maria Oliani, Luiz Ricardo GoulartAbstractBreast Cancer (BC) is a highly heterogeneous disease whose most aggressive behavior is di...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - July 11, 2018 Category: Molecular Biology Source Type: research

SIRT2 reduces actin polymerization and cell migration through deacetylation and degradation of HSP90
Publication date: September 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Volume 1865, Issue 9Author(s): Jung Sun Min, Jin Chul Kim, Ji Ae Kim, Inho Kang, Jeong Keun AhnAbstractSIRT2, a member of the class III histone deacetylase family, has been identified as a tumor suppressor, which is associated with various cellular processes including metabolism and proliferation. However, the effects of SIRT2 on cancer cell migration caused by cytoskeletal rearrangement remain uncertain. Here we show that SIRT2 inhibits cell motility by suppressing actin polymerization. SIRT2 regulates actin dynamics thr...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - July 11, 2018 Category: Molecular Biology Source Type: research

Structural bases of the assembly, recognition and disassembly of linear ubiquitin chain
Publication date: Available online 5 July 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Cell ResearchAuthor(s): Jianping Liu, Lifeng PanAbstractLinear ubiquitin chain is a latest discovered type of poly-ubiquitin chain that is broadly involved in innate immune and inflammatory pathways. Dysfunctions in its assembly, recognition or disassembly are intimately related with numerous immunodeficiency or autoimmune diseases. Our understanding of the molecular mechanism for linear ubiquitin chain formation, recognition and disassembly has being significantly evolved in recent years, with particular contribution from...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - July 6, 2018 Category: Molecular Biology Source Type: research

Sphingolipid-mediated calcium signaling and its pathological effects
Publication date: Available online 26 April 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Cell ResearchAuthor(s): Ilari Pulli, Muhammad Yasir Asghar, Kati Kemppainen, Kid TörnquistAbstractMetabolites of sphingomyelin, as well as calcium ion fluxes, have a profound role in cellular signaling in almost all cell types. In addition, metabolites of sphingomyelin often modulate calcium signaling, either directly or indirectly. This is an interesting aspect on how lipids may wield their physiological role, as calcium is probably one of the most versatile signaling molecules in the cell, and as modulation of cal...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - July 5, 2018 Category: Molecular Biology Source Type: research

Two-pore channels and disease
Publication date: Available online 7 May 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Cell ResearchAuthor(s): Sandip Patel, Bethan S. KilpatrickAbstractTwo-pore channels (TPCs) are Ca2+-permeable endo-lysosomal ion channels subject to multi-modal regulation. They mediate their physiological effects through releasing Ca2+ from acidic organelles in response to cues such as the second messenger, NAADP. Here, we review emerging evidence linking TPCs to disease. We discuss how perturbing both local and global Ca2+ changes mediated by TPCs through chemical and/or molecular manipulations can induce or reverse disea...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - July 5, 2018 Category: Molecular Biology Source Type: research

The role of Ca2+ in oocyte activation during In Vitro fertilization: Insights into potential therapies for rescuing failed fertilization
Publication date: Available online 8 May 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Cell ResearchAuthor(s): Karl SwannAbstractAt fertilization the mature mammalian oocyte is activated to begin development by a sperm-induced series of increases in the cytosolic free Ca2+ concentration. These so called Ca2+ oscillations, or repetitive Ca2+ spikes, are also seen after intracytoplasmic sperm injection (ICSI) and are primarily triggered by a sperm protein called phospholipase Czeta (PLCζ). Whilst ICSI is generally an effective way to fertilizing human oocytes, there are cases where oocyte activation fails ...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - July 5, 2018 Category: Molecular Biology Source Type: research

NCS-1 is a regulator of calcium signaling in health and disease
The objective of this article is to summarize the current body of evidence describing NCS-1 and its interactions on a molecular and cellular scale, as well as describing macroscopic implications in physiology and medicine. Particular attention is paid to the role of NCS-1 in development and prevention of chemotherapy induced peripheral neuropathy (CIPN). (Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research)
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - July 5, 2018 Category: Molecular Biology Source Type: research

Altered Ca2+ signaling in enamelopathies
Publication date: Available online 9 May 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Cell ResearchAuthor(s): Miriam Eckstein, Francisco J. Aulestia, Meerim K. Nurbaeva, Rodrigo S. LacruzAbstractBiomineralization requires the controlled movement of ions across cell barriers to reach the sites of crystal growth. Mineral precipitation occurs in aqueous phases as fluids become supersaturated with specific ionic compositions. In the biological world, biomineralization is dominated by the presence of calcium (Ca2+) in crystal lattices. Ca2+ channels are intrinsic modulators of this process, facilitating the avail...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - July 5, 2018 Category: Molecular Biology Source Type: research

Ca2+ signaling and spinocerebellar ataxia
Publication date: Available online 16 May 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Cell ResearchAuthor(s): Chihiro Hisatsune, Kozo Hamada, Katsuhiko MikoshibaAbstractSpinocerebellar ataxia (SCA) is a neural disorder, which is caused by degenerative changes in the cerebellum. SCA is primarily characterized by gait ataxia, and additional clinical features include nystagmus, dysarthria, tremors and cerebellar atrophy. Forty-four hereditary SCAs have been identified to date, along with>35 SCA-associated genes. Despite the great diversity and distinct functionalities of the SCA-related genes, accumulating ...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - July 5, 2018 Category: Molecular Biology Source Type: research

Regulation of bile secretion by calcium signaling in health and disease
Publication date: Available online 19 May 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Cell ResearchAuthor(s): David C. Trampert, Michael H. NathansonAbstractCalcium (Ca2+) signaling controls secretion in many types of cells and tissues. In the liver, Ca2+ regulates secretion in both hepatocytes, which are responsible for primary formation of bile, and cholangiocytes, which line the biliary tree and further condition the bile before it is secreted. Cholestatic liver diseases, which are characterized by impaired bile secretion, may result from impaired Ca2+ signaling mechanisms in either hepatocytes or cholan...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - July 5, 2018 Category: Molecular Biology Source Type: research