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Full-Text Articles in Life Sciences
Stomatin-Like Protein 2 Deficiency In T Cells Is Associated With Altered Mitochondrial Respiration And Defective Cd4+ T Cell Responses., Darah A Christie, Panagiotis Mitsopoulos, Julianna Blagih, Stanley D Dunn, Julie St-Pierre, Russell G Jones, Grant M Hatch, Joaquín Madrenas
Stomatin-Like Protein 2 Deficiency In T Cells Is Associated With Altered Mitochondrial Respiration And Defective Cd4+ T Cell Responses., Darah A Christie, Panagiotis Mitsopoulos, Julianna Blagih, Stanley D Dunn, Julie St-Pierre, Russell G Jones, Grant M Hatch, Joaquín Madrenas
Stanley D Dunn
Stomatin-like protein 2 (SLP-2) is a mostly mitochondrial protein that regulates mitochondrial biogenesis and function and modulates T cell activation. To determine the mechanism of action of SLP-2, we generated T cell-specific SLP-2-deficient mice. These mice had normal numbers of thymocytes and T cells in the periphery. However, conventional SLP-2-deficient T cells had a posttranscriptional defect in IL-2 production in response to TCR ligation, and this translated into reduced CD4(+) T cell responses. SLP-2 deficiency was associated with impaired cardiolipin compartmentalization in mitochondrial membranes, decreased levels of the NADH dehydrogenase (ubiquinone) iron-sulfur protein 3, NADH dehydrogenase (ubiquinone) 1β subcomplex subunit …
Supervillin-Mediated Suppression Of P53 Protein Enhances Cell Survival, Zhiyou Fang, Elizabeth Luna
Supervillin-Mediated Suppression Of P53 Protein Enhances Cell Survival, Zhiyou Fang, Elizabeth Luna
Elizabeth J. Luna
Integrin-based adhesions promote cell survival as well as cell motility and invasion. We show here that the adhesion regulatory protein supervillin increases cell survival by decreasing levels of the tumor suppressor protein p53 and downstream target genes. RNAi-mediated knockdown of a new splice form of supervillin (isoform 4) or both isoforms 1 and 4 increases the amount of p53 and cell death, whereas p53 levels decrease after overexpression of either supervillin isoform. Cellular responses to DNA damage induced by etoposide or doxorubicin include down-regulation of endogenous supervillin coincident with increases in p53. In DNA-damaged supervillin knockdown cells, p53 knockdown or …
An N-Terminal, 830 Residues Intrinsically Disordered Region Of The Cytoskeleton-Regulatory Protein Supervillin Contains Myosin Ii- And F-Actin-Binding Sites, Stanislav Fedechkin, Jacob Brockerman, Elizabeth Luna, Michail Lobanov, Oxana Galzitskaya, Serge Smirnov
An N-Terminal, 830 Residues Intrinsically Disordered Region Of The Cytoskeleton-Regulatory Protein Supervillin Contains Myosin Ii- And F-Actin-Binding Sites, Stanislav Fedechkin, Jacob Brockerman, Elizabeth Luna, Michail Lobanov, Oxana Galzitskaya, Serge Smirnov
Elizabeth J. Luna
Supervillin, the largest member of the villin/gelsolin family, is a cytoskeleton regulating, peripheral membrane protein. Supervillin increases cell motility and promotes invasive activity in tumors. Major cytoskeletal interactors, including filamentous actin and myosin II, bind within the unique supervillin amino terminus, amino acids 1-830. The structural features of this key region of the supervillin polypeptide are unknown. Here, we utilize circular dichroism and bioinformatics sequence analysis to demonstrate that the N-terminal part of supervillin forms an extended intrinsically disordered region (IDR). Our combined data indicate that the N-terminus of human and bovine supervillin sequences (positions 1-830) represents an IDR, which …
Human Genome-Wide Association And Mouse Knockout Approaches Identify Platelet Supervillin As An Inhibitor Of Thrombus Formation Under Shear Stress, Leonard Edelstein, Elizabeth Luna, Ian Gibson, Molly Bray, Ying Jin, Altaf Kondkar, Srikanth Nagalla, Nacima Hadjout-Rabi, Tara Smith, Daniel Covarrubias, Stephen Jones, Firdos Ahmad, Moritz Stolla, Xianguo Kong, Zhiyou Fang, Wolfgang Bergmeier, Chad Shaw, Suzanne Leal, Paul Bray
Human Genome-Wide Association And Mouse Knockout Approaches Identify Platelet Supervillin As An Inhibitor Of Thrombus Formation Under Shear Stress, Leonard Edelstein, Elizabeth Luna, Ian Gibson, Molly Bray, Ying Jin, Altaf Kondkar, Srikanth Nagalla, Nacima Hadjout-Rabi, Tara Smith, Daniel Covarrubias, Stephen Jones, Firdos Ahmad, Moritz Stolla, Xianguo Kong, Zhiyou Fang, Wolfgang Bergmeier, Chad Shaw, Suzanne Leal, Paul Bray
Elizabeth J. Luna
BACKGROUND: High shear force critically regulates platelet adhesion and thrombus formation during ischemic vascular events. To identify genetic factors that influence platelet thrombus formation under high shear stress, we performed a genome-wide association study (GWAS) and confirmatory experiments in human and animal platelets. METHODS AND RESULTS: Closure times in the shear-dependent Platelet Function Analyzer (PFA)-100® were measured on healthy, non-diabetic European Americans (n=125) and African Americans (n=116). A GWAS significant association (p<5X10(-8)) was identified with 2 SNPs within the SVIL gene (chr 10p11.23) in African-Americans but not European Americans. Microarray analyses of human platelet RNA demonstrated the presence of …
Novel Interactors And A Role For Supervillin In Early Cytokinesis, Tara Smith, Zhiyou Fang, Elizabeth Luna
Novel Interactors And A Role For Supervillin In Early Cytokinesis, Tara Smith, Zhiyou Fang, Elizabeth Luna
Elizabeth J. Luna
Supervillin, the largest member of the villin/gelsolin/flightless family, is a peripheral membrane protein that regulates each step of cell motility, including cell spreading. Most known interactors bind within its amino (N)-terminus. We show here that the supervillin carboxy (C)-terminus can be modeled as supervillin-specific loops extending from gelsolin-like repeats plus a villin-like headpiece. We have identified 27 new candidate interactors from yeast two-hybrid screens. The interacting sequences from 12 of these proteins (BUB1, EPLIN/LIMA1, FLNA, HAX1, KIF14, KIFC3, MIF4GD/SLIP1, ODF2/Cenexin, RHAMM, STARD9/KIF16A, Tks5/SH3PXD2A, TNFAIP1) co-localize with and mis-localize EGFP-supervillin in mammalian cells, suggesting associations in vivo. Supervillin-interacting sequences within BUB1, …
The Membrane-Associated Protein, Supervillin, Accelerates F-Actin-Dependent Rapid Integrin Recycling And Cell Motility, Zhiyou Fang, Norio Takizawa, Korey Wilson, Tara Smith, Anna Delprato, Michael Davidson, David Lambright, Elizabeth Luna
The Membrane-Associated Protein, Supervillin, Accelerates F-Actin-Dependent Rapid Integrin Recycling And Cell Motility, Zhiyou Fang, Norio Takizawa, Korey Wilson, Tara Smith, Anna Delprato, Michael Davidson, David Lambright, Elizabeth Luna
Elizabeth J. Luna
In migrating cells, the cytoskeleton coordinates signal transduction and redistribution of transmembrane proteins, including integrins and growth factor receptors. Supervillin is an F-actin- and myosin II-binding protein that tightly associates with signaling proteins in cholesterol-rich, 'lipid raft' membrane microdomains. We show here that supervillin also can localize with markers for early and sorting endosomes (EE/SE) and with overexpressed components of the Arf6 recycling pathway in the cell periphery. Supervillin tagged with the photoswitchable fluorescent protein, tdEos, moves both into and away from dynamic structures resembling podosomes at the basal cell surface. Rapid integrin recycling from EE/SE is inhibited in supervillin-knockdown …