Document Detail


A novel juxtamembrane domain in tumor necrosis factor receptor superfamily molecules activates Rac1 and controls neurite growth.
MedLine Citation:
PMID:  18508927     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Members of the tumor necrosis factor receptor (TNFR) superfamily control cell fate determination, including cell death and differentiation. Fas (CD95) is the prototypical "death receptor" of the TNFR superfamily and signals apoptosis through well established pathways. In the adult nervous system, Fas induces apoptosis in the context of neuropathology such as stroke or amyotrophic lateral sclerosis. However, during nervous system development, Fas promotes neurite growth and branching. The molecular mechanisms underlying Fas-induced process formation and branching have remained unknown to date. Here, we define the molecular pathway linking Fas to process growth and branching in cell lines and in developing neurons. We describe a new cytoplasmic membrane proximal domain (MPD) that is essential for Fas-induced process growth and that is conserved in members of the TNFR superfamily. We show that the Fas MPD recruits ezrin, a molecule that links transmembrane proteins to the cytoskeleton, and activates the small GTPase Rac1. Deletion of the MPD, but not the death domain, abolished Rac1 activation and process growth. Furthermore, an ezrin-derived inhibitory peptide prevented Fas-induced neurite growth in primary neurons. Our results define a new domain, topologically and functionally distinct from the death domain, which regulates neuritogenesis via recruitment of ezrin and activation of Rac1.
Authors:
Wenjing Ruan; Christopher T Lee; Julie Desbarats
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-05-28
Journal Detail:
Title:  Molecular biology of the cell     Volume:  19     ISSN:  1939-4586     ISO Abbreviation:  Mol. Biol. Cell     Publication Date:  2008 Aug 
Date Detail:
Created Date:  2008-07-29     Completed Date:  2008-12-22     Revised Date:  2013-06-05    
Medline Journal Info:
Nlm Unique ID:  9201390     Medline TA:  Mol Biol Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3192-202     Citation Subset:  IM    
Affiliation:
Department of Physiology, McGill University, Montréal, Québec H3G 1Y6, Canada.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, CD95 / biosynthesis,  chemistry*
COS Cells
Cell Line, Tumor
Cercopithecus aethiops
Cytoplasm / metabolism
Cytoskeletal Proteins / metabolism*
Gene Expression Regulation*
Humans
Models, Biological
Neurites / metabolism*
Neurons / metabolism
Protein Structure, Tertiary
Receptors, Tumor Necrosis Factor / metabolism*
rac1 GTP-Binding Protein / metabolism*
Chemical
Reg. No./Substance:
0/Antigens, CD95; 0/Cytoskeletal Proteins; 0/RAC1 protein, human; 0/Receptors, Tumor Necrosis Factor; 0/ezrin; EC 3.6.5.2/rac1 GTP-Binding Protein
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