| Vesicular trafficking through cortical actin during exocytosis is regulated by the Rab27a effector JFC1/Slp1 and the RhoA-GTPase-activating protein Gem-interacting protein. | |
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MedLine Citation:
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PMID: 22438581 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cytoskeleton remodeling is important for the regulation of vesicular transport associated with exocytosis, but a direct association between granular secretory proteins and actin-remodeling molecules has not been shown, and this mechanism remains obscure. Using a proteomic approach, we identified the RhoA-GTPase-activating protein Gem-interacting protein (GMIP) as a factor that associates with the Rab27a effector JFC1 and modulates vesicular transport and exocytosis. GMIP down-regulation induced RhoA activation and actin polymerization. Importantly, GMIP-down-regulated cells showed impaired vesicular transport and exocytosis, while inhibition of the RhoA-signaling pathway induced actin depolymerization and facilitated exocytosis. We show that RhoA activity polarizes around JFC1-containing secretory granules, suggesting that it may control directionality of granule movement. Using quantitative live-cell microscopy, we show that JFC1-containing secretory organelles move in areas near the plasma membrane deprived of polymerized actin and that dynamic vesicles maintain an actin-free environment in their surroundings. Supporting a role for JFC1 in RhoA inactivation and actin remodeling during exocytosis, JFC1 knockout neutrophils showed increased RhoA activity, and azurophilic granules were unable to traverse cortical actin in cells lacking JFC1. We propose that during exocytosis, actin depolymerization commences near the secretory organelle, not the plasma membrane, and that secretory granules use a JFC1- and GMIP-dependent molecular mechanism to traverse cortical actin. |
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Authors:
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Jennifer L Johnson; Jlenia Monfregola; Gennaro Napolitano; William B Kiosses; Sergio D Catz |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2012-03-21 |
Journal Detail:
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Title: Molecular biology of the cell Volume: 23 ISSN: 1939-4586 ISO Abbreviation: Mol. Biol. Cell Publication Date: 2012 May |
Date Detail:
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Created Date: 2012-05-14 Completed Date: 2012-09-10 Revised Date: 2012-09-25 |
Medline Journal Info:
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Nlm Unique ID: 9201390 Medline TA: Mol Biol Cell Country: United States |
Other Details:
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Languages: eng Pagination: 1902-16 Citation Subset: IM |
Affiliation:
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Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, CA 92037, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Actin Cytoskeleton
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metabolism Amino Acid Sequence Animals Cell Line, Tumor Exocytosis GTPase-Activating Proteins / genetics, metabolism* Granulocytes / metabolism, secretion Humans Membrane Proteins / genetics, metabolism* Mice Mice, Inbred C57BL Mice, Knockout Molecular Sequence Data Neutrophils / metabolism, secretion, ultrastructure Primary Cell Culture Protein Binding Protein Multimerization Secretory Pathway* Secretory Vesicles / metabolism*, ultrastructure Signal Transduction rab GTP-Binding Proteins / metabolism* rhoA GTP-Binding Protein / metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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HL088256/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/GMIP protein, human; 0/GTPase-Activating Proteins; 0/JFC1 protein, human; 0/Membrane Proteins; EC 3.6.1.-/rab GTP-Binding Proteins; EC 3.6.1.-./RAB27A protein, human; EC 3.6.5.2/rhoA GTP-Binding Protein |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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