A Novel,Retromer‐Independent Role for Sorting Nexins 1 and 2 in RhoG‐Dependent Membrane Remodeling |
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| Authors: | Derek C Prosser Duvinh Tran Allana Schooley Beverly Wendland Johnny K Ngsee |
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| Institution: | 1. Department of Cellular and Molecular Medicine, Ottawa Hospital Research Institute, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, K1H 8M5, Canada;2. Department of Biology, The Johns Hopkins University, 3400 N. Charles Street, Baltimore, MD 21218, USA |
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| Abstract: | The sorting nexins SNX1 and SNX2 are members of the retromer complex involved in protein sorting within the endocytic pathway. While retromer‐dependent functions of SNX1 and SNX2 have been well documented, potential retromer‐independent roles remain unclear. Here, we show that SNX1 and SNX2 interact with the Rac1 and RhoG guanine nucleotide exchange factor Kalirin‐7. Simultaneous overexpression of SNX1 or SNX2 and Kalirin‐7 in epithelial cells causes partial redistribution of both SNX isoforms to the plasma membrane, and results in RhoG‐dependent lamellipodia formation that requires functional Phox homology (PX) and Bin/Amphiphysin/Rvs (BAR) domains of SNX, but is Rac1‐ and retromer‐independent. Conversely, depletion of endogenous SNX1 or SNX2 inhibits Kalirin‐7‐mediated lamellipodia formation. Finally, we demonstrate that SNX1 and SNX2 interact directly with inactive RhoG, suggesting a novel role for these SNX proteins in recruiting an inactive Rho GTPase to its exchange factor. |
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| Keywords: | actin BAR domain Kalirin lamellipodia membrane remodeling retromer RhoG sorting nexin |
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