Document Detail

Delivery of the CSF-1R to the lumen of macropinosomes promotes its destruction in macrophages.
MedLine Citation:
PMID:  25335894     Owner:  NLM     Status:  Publisher    
Activation of the macrophage Colony Stimulating Factor-1 Receptor (CSF-1R) by CSF-1 stimulates pronounced macropinocytosis and drives proliferation of macrophages. While the role of macropinocytosis in CSF-1R signaling remains unknown, we show that despite internalizing large quantities of plasma membrane, macropinosomes contribute little to the internalization of the CSF-1/CSF-1R complex. Rather, internalization of the CSF-1R in small, endocytic vesicles, sensitive to clathrin disruption, out-compete macropinosomes for CSF-1R endocytosis. Following internalization, small vesicles carrying the CSF-1R underwent homotypic fusion and then trafficked to newly formed macropinosomes bearing Rab5. As these macropinosomes matured, acquiring Rab7, the CSF-1R was transported into their lumen, and degraded. Inhibition of macropinocytosis delayed receptor degradation despite no disruption of CSF-1R endocytosis. These data indicate that CSF-1-stimulated macropinosomes are sites of multivesicular body formation and accelerate CSF-1R degradation. Further, we demonstrate that macropinocytosis and cell growth have a matching dose dependence on CSF-1, suggesting that macropinosomes may be a central mechanism coupling CSF-1R signaling and macrophage growth.
Jieqiong Lou; Shalini T Low-Nam; Jason G Kerkvliet; Adam D Hoppe
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-10-21
Journal Detail:
Title:  Journal of cell science     Volume:  -     ISSN:  1477-9137     ISO Abbreviation:  J. Cell. Sci.     Publication Date:  2014 Oct 
Date Detail:
Created Date:  2014-10-22     Completed Date:  -     Revised Date:  2014-10-23    
Medline Journal Info:
Nlm Unique ID:  0052457     Medline TA:  J Cell Sci     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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