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Full-Text Articles in Medicine and Health Sciences
A Mutation In The Mouse Chd2 Chromatin Remodeling Enzyme Results In A Complex Renal Phenotype, Concetta Marfella, Nils Henninger, Scott Leblanc, Namrata Krishnan, David Garlick, Lawrence Holzman, Anthony Imbalzano
A Mutation In The Mouse Chd2 Chromatin Remodeling Enzyme Results In A Complex Renal Phenotype, Concetta Marfella, Nils Henninger, Scott Leblanc, Namrata Krishnan, David Garlick, Lawrence Holzman, Anthony Imbalzano
Nils Henninger
BACKGROUND AND AIMS: Glomerular diseases are the third leading cause of kidney failure worldwide, behind only diabetes and hypertension. The molecular mechanisms underlying the cause of glomerular diseases are still largely unknown. The identification and characterization of new molecules associated with glomerular function should provide new insights into understanding the diverse group of glomerular diseases. The Chd2 protein belongs to a family of enzymes involved in ATP-dependent chromatin remodeling, suggesting that it likely functions as an epigenetic regulator of gene expression via the modification of chromatin structure. METHODS: In this study, we present a detailed histomorphologic characterization of mice containing …
Sting-Irf3 Pathway Links Endoplasmic Reticulum Stress With Hepatocyte Apoptosis In Early Alcoholic Liver Disease, Jan Petrasek, Arvin Iracheta-Vellve, Timea Csak, Abhishek Satishchandran, Karen Kodys, Evelyn A. Kurt-Jones, Katherine A. Fitzgerald, Gyongyi Szabo
Sting-Irf3 Pathway Links Endoplasmic Reticulum Stress With Hepatocyte Apoptosis In Early Alcoholic Liver Disease, Jan Petrasek, Arvin Iracheta-Vellve, Timea Csak, Abhishek Satishchandran, Karen Kodys, Evelyn A. Kurt-Jones, Katherine A. Fitzgerald, Gyongyi Szabo
Katherine A. Fitzgerald
Emerging evidence suggests that innate immunity drives alcoholic liver disease (ALD) and that the interferon regulatory factor 3 (IRF3),a transcription factor regulating innate immune responses, is indispensable for the development of ALD. Here we report that IRF3 mediates ALD via linking endoplasmic reticulum (ER) stress with apoptotic signaling in hepatocytes. We found that ethanol induced ER stress and triggered the association of IRF3 with the ER adaptor, stimulator of interferon genes (STING), as well as subsequent phosphorylation of IRF3. Activated IRF3 associated with the proapoptotic molecule Bax [B-cell lymphoma 2 (Bcl2)-associated X protein] and contributed to hepatocyte apoptosis. Deficiency of …
Sting-Irf3 Pathway Links Endoplasmic Reticulum Stress With Hepatocyte Apoptosis In Early Alcoholic Liver Disease, Jan Petrasek, Arvin Iracheta-Vellve, Timea Csak, Abhishek Satishchandran, Karen Kodys, Evelyn A. Kurt-Jones, Katherine A. Fitzgerald, Gyongyi Szabo
Sting-Irf3 Pathway Links Endoplasmic Reticulum Stress With Hepatocyte Apoptosis In Early Alcoholic Liver Disease, Jan Petrasek, Arvin Iracheta-Vellve, Timea Csak, Abhishek Satishchandran, Karen Kodys, Evelyn A. Kurt-Jones, Katherine A. Fitzgerald, Gyongyi Szabo
Gyongyi Szabo
Emerging evidence suggests that innate immunity drives alcoholic liver disease (ALD) and that the interferon regulatory factor 3 (IRF3),a transcription factor regulating innate immune responses, is indispensable for the development of ALD. Here we report that IRF3 mediates ALD via linking endoplasmic reticulum (ER) stress with apoptotic signaling in hepatocytes. We found that ethanol induced ER stress and triggered the association of IRF3 with the ER adaptor, stimulator of interferon genes (STING), as well as subsequent phosphorylation of IRF3. Activated IRF3 associated with the proapoptotic molecule Bax [B-cell lymphoma 2 (Bcl2)-associated X protein] and contributed to hepatocyte apoptosis. Deficiency of …
Pubertal And Adult Leydig Cell Function In Mullerian Inhibiting Substance-Deficient Mice, Xiufeng Wu, Ramamani Arumugam, Stephen Baker, Mary Lee
Pubertal And Adult Leydig Cell Function In Mullerian Inhibiting Substance-Deficient Mice, Xiufeng Wu, Ramamani Arumugam, Stephen Baker, Mary Lee
Mary M. Lee
Mullerian inhibiting substance (MIS) causes Mullerian duct regression during sexual differentiation and regulates postnatal Leydig cell development. MIS knockout (MIS-KO) mice with targeted deletions of MIS develop Leydig cell hyperplasia, but their circulating androgen concentrations are reportedly unaltered. We compared reproductive hormone profiles, androgen biosynthesis, and the expression of key steroidogenic and metabolic enzymes in MIS-KO and wild-type (WT) mice at puberty (36 d) and sexual maturity (60 d). In pubertal animals, basal testosterone and LH concentrations in plasma were lower in MIS-KO than WT mice, whereas human chorionic gonadotropin-stimulated testosterone concentrations were similar. In adults, basal LH, and both …
Supervillin Slows Cell Spreading By Facilitating Myosin Ii Activation At The Cell Periphery, Norio Takizawa, Reiko Ikebe, Mitsuo Ikebe, Elizabeth J. Luna
Supervillin Slows Cell Spreading By Facilitating Myosin Ii Activation At The Cell Periphery, Norio Takizawa, Reiko Ikebe, Mitsuo Ikebe, Elizabeth J. Luna
Elizabeth J. Luna
During cell migration, myosin II modulates adhesion, cell protrusion and actin organization at the leading edge. We show that an F-actin- and membrane-associated scaffolding protein, called supervillin (SV, p205), binds directly to the subfragment 2 domains of nonmuscle myosin IIA and myosin IIB and to the N-terminus of the long form of myosin light chain kinase (L-MLCK). SV inhibits cell spreading via an MLCK- and myosin II-dependent mechanism. Overexpression of SV reduces the rate of cell spreading, and RNAi-mediated knockdown of endogenous SV increases it. Endogenous and EGFP-tagged SV colocalize with, and enhance the formation of, cortical bundles of F-actin …
Merlin Differs From Moesin In Binding To F-Actin And In Its Intra- And Intermolecular Interactions, L. Huang, E. Ichimaru, Kersi Pestonjamasp, X. Cui, H. Nakamura, G. Lo, F. Lin, Elizabeth Luna, H. Furthmayr
Merlin Differs From Moesin In Binding To F-Actin And In Its Intra- And Intermolecular Interactions, L. Huang, E. Ichimaru, Kersi Pestonjamasp, X. Cui, H. Nakamura, G. Lo, F. Lin, Elizabeth Luna, H. Furthmayr
Elizabeth J. Luna
The neurofibromatosis type 2 (NF2) tumor suppressor gene encodes merlin, a protein with homology to the cell membrane/F-actin linking proteins, moesin, ezrin and radixin. Unlike these closely related proteins, merlin lacks a C-terminal F-actin binding site detectable by actin blot overlays, and the GFP-tagged merlin C-terminal domain co-distributes with neither stress fibers nor cortical actin in NIH3T3 cells. Merlin also differs from the other three proteins in its inter- and intramolecular domain interactions, as shown by in vitro binding and yeast two-hybrid assays. As is true for ezrin, moesin and radixin, the N- and C-terminal domains of merlin type 1 …
Supervillin Modulation Of Focal Adhesions Involving Trip6/Zrp-1, Norio Takizawa, Tara C. Smith, Thomas Nebl, Jessica Lynn Crowley, Stephen J. Palmieri, Lawrence M. Lifshitz, Anka G. Ehrhardt, Laura M. Hoffman, Mary C. Beckerle, Elizabeth J. Luna
Supervillin Modulation Of Focal Adhesions Involving Trip6/Zrp-1, Norio Takizawa, Tara C. Smith, Thomas Nebl, Jessica Lynn Crowley, Stephen J. Palmieri, Lawrence M. Lifshitz, Anka G. Ehrhardt, Laura M. Hoffman, Mary C. Beckerle, Elizabeth J. Luna
Elizabeth J. Luna
Cell-substrate contacts, called focal adhesions (FAs), are dynamic in rapidly moving cells. We show that supervillin (SV)--a peripheral membrane protein that binds myosin II and F-actin in such cells--negatively regulates stress fibers, FAs, and cell-substrate adhesion. The major FA regulatory sequence within SV (SV342-571) binds to the LIM domains of two proteins in the zyxin family, thyroid receptor-interacting protein 6 (TRIP6) and lipoma-preferred partner (LPP), but not to zyxin itself. SV and TRIP6 colocalize within large FAs, where TRIP6 may help recruit SV. RNAi-mediated decreases in either protein increase cell adhesion to fibronectin. TRIP6 partially rescues SV effects on stress …
Archvillin, A Muscle-Specific Isoform Of Supervillin, Is An Early Expressed Component Of The Costameric Membrane Skeleton, Sang W. Oh, Robert K. Pope, Kelly P. Smith, Jessica Lynn Crowley, Thomas Nebl, Jeanne B. Lawrence, Elizabeth J. Luna
Archvillin, A Muscle-Specific Isoform Of Supervillin, Is An Early Expressed Component Of The Costameric Membrane Skeleton, Sang W. Oh, Robert K. Pope, Kelly P. Smith, Jessica Lynn Crowley, Thomas Nebl, Jeanne B. Lawrence, Elizabeth J. Luna
Elizabeth J. Luna
The membrane skeleton protein supervillin binds tightly to both F-actin and membranes and can potentiate androgen receptor activity in non-muscle cells. We report that muscle, which constitutes the principal tissue source for supervillin sequences, contains a approximately 250 kDa isoform of supervillin that localizes within nuclei and with dystrophin at costameres, regions of F-actin membrane attachment in skeletal muscle. The gene encoding this protein, 'archvillin' (Latin, archi; Greek, archos; 'principal' or 'chief'), contains an evolutionarily conserved, muscle-specific 5' leader sequence. Archvillin cDNAs also contain four exons that encode approximately 47 kDa of additional muscle-specific protein sequence in the form of …