Document Detail


Unexpected requirement for ELMO1 in clearance of apoptotic germ cells in vivo.
MedLine Citation:
PMID:  20844538     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Apoptosis and the subsequent clearance of dying cells occurs throughout development and adult life in many tissues. Failure to promptly clear apoptotic cells has been linked to many diseases. ELMO1 is an evolutionarily conserved cytoplasmic engulfment protein that functions downstream of the phosphatidylserine receptor BAI1, and, along with DOCK1 and the GTPase RAC1, promotes internalization of the dying cells. Here we report the generation of ELMO1-deficient mice, which we found to be unexpectedly viable and grossly normal. However, they had a striking testicular pathology, with disrupted seminiferous epithelium, multinucleated giant cells, uncleared apoptotic germ cells and decreased sperm output. Subsequent in vitro and in vivo analyses revealed a crucial role for ELMO1 in the phagocytic clearance of apoptotic germ cells by Sertoli cells lining the seminiferous epithelium. The engulfment receptor BAI1 and RAC1 (upstream and downstream of ELMO1, respectively) were also important for Sertoli-cell-mediated engulfment. Collectively, these findings uncover a selective requirement for ELMO1 in Sertoli-cell-mediated removal of apoptotic germ cells and make a compelling case for a relationship between engulfment and tissue homeostasis in vivo.
Authors:
Michael R Elliott; Shuqiu Zheng; Daeho Park; Robin I Woodson; Michael A Reardon; Ignacio J Juncadella; Jason M Kinchen; Jun Zhang; Jeffrey J Lysiak; Kodi S Ravichandran
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Nature     Volume:  467     ISSN:  1476-4687     ISO Abbreviation:  Nature     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-09-16     Completed Date:  2010-10-15     Revised Date:  2013-09-18    
Medline Journal Info:
Nlm Unique ID:  0410462     Medline TA:  Nature     Country:  England    
Other Details:
Languages:  eng     Pagination:  333-7     Citation Subset:  IM    
Affiliation:
Beirne B. Carter Center for Immunology Research, University of Virginia, Charlottesville, Virginia 22908, USA.
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MeSH Terms
Descriptor/Qualifier:
Adaptor Proteins, Signal Transducing / deficiency,  genetics,  metabolism*
Angiogenic Proteins / metabolism
Animals
Apoptosis*
Cell Line
Homeostasis
Male
Mice
Mice, Inbred C57BL
Neuropeptides / metabolism
Phagocytosis / physiology*
Phosphatidylserines / metabolism
Seminiferous Epithelium / cytology,  pathology
Sertoli Cells / cytology*,  metabolism*,  pathology
Signal Transduction
Spermatozoa / cytology*,  pathology
rac GTP-Binding Proteins / metabolism
Grant Support
ID/Acronym/Agency:
R01 GM064709/GM/NIGMS NIH HHS; R01 HD057242/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/Adaptor Proteins, Signal Transducing; 0/Angiogenic Proteins; 0/Bai1 protein, mouse; 0/ELMO1 protein, mouse; 0/Neuropeptides; 0/Phosphatidylserines; 0/Rac1 protein, mouse; EC 3.6.5.2/rac GTP-Binding Proteins
Comments/Corrections

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