| SNX9 activities are regulated by multiple phosphoinositides through both PX and BAR domains. | |
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MedLine Citation:
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PMID: 17988218 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Sorting nexin 9 (SNX9) functions at the interface between membrane remodeling and the actin cytoskeleton. In particular, SNX9 links membrane binding to potentiation of N-WASP and dynamin GTPase activities. SNX9 is one of a growing number of proteins that contain two lipid-binding domains, a phox homology (PX) and a Bin1/Amphiphysin/RVS167 (BAR) domain, and localizes to diverse membranes that are enriched in different phosphoinositides. Here, we investigate the mechanism by which SNX9 functions at these varied membrane environments. We show that SNX9 has low-lipid-binding affinity and harnesses a broad range of phosphoinositides to synergistically enhance both dynamin and N-WASP activities. We introduced point mutations in either the PX domain, BAR domain or both that are predicted to disrupt their functions and examined their respective roles in lipid-binding, and dynamin and N-WASP activation. We show that the broad lipid specificity of SNX9 is not because of independent and additive contributions by individual domains. Rather, the two domains appear to function in concert to confer lipid-binding and SNX9's membrane active properties. We also demonstrate that the two domains are differentially required for full SNX9 activity in N-WASP and dynamin regulation, and for localization of SNX9 to clathrin-coated pits and dorsal ruffles. In total, our results suggest that SNX9 can integrate signals from varied lipids through two domains to direct membrane remodeling events at multiple cellular locations. |
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Authors:
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Defne Yarar; Mark C Surka; Marilyn C Leonard; Sandra L Schmid |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2007-11-13 |
Journal Detail:
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Title: Traffic (Copenhagen, Denmark) Volume: 9 ISSN: 1398-9219 ISO Abbreviation: Traffic Publication Date: 2008 Jan |
Date Detail:
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Created Date: 2007-12-24 Completed Date: 2008-04-09 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100939340 Medline TA: Traffic Country: Denmark |
Other Details:
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Languages: eng Pagination: 133-46 Citation Subset: IM |
Affiliation:
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Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. yarar@wi.mit.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Actins
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metabolism Animals Cell Line Clathrin-Coated Vesicles / metabolism Dynamins / metabolism Escherichia coli / genetics Fibroblasts / metabolism Humans Liposomes Mice Microfilaments / ultrastructure Microscopy, Electron Phosphatidylinositols / metabolism* Point Mutation Protein Binding Protein Interaction Domains and Motifs* Vesicular Transport Proteins / genetics, metabolism* Wiskott-Aldrich Syndrome Protein, Neuronal / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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GM31645/GM/NIGMS NIH HHS; GM42455/GM/NIGMS NIH HHS; MH61345/MH/NIMH NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Actins; 0/Liposomes; 0/Phosphatidylinositols; 0/SNX9 protein, human; 0/Vesicular Transport Proteins; 0/Wiskott-Aldrich Syndrome Protein, Neuronal; EC 3.6.5.5/Dynamins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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