A novel, retromer-independent role for sorting nexins 1 and 2 in RhoG-dependent membrane remodeling.
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.
Prosser
Derek C
DC
Department of Cellular and Molecular Medicine, Ottawa Hospital Research Institute, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, K1H 8M5, Canada.
Tran
Duvinh
D
Schooley
Allana
A
Wendland
Beverly
B
Ngsee
Johnny K
JK
D000199:Actins / Q000378:metabolism; D000818:Animals; D019556:COS Cells; D002462:Cell Membrane / Q000378:metabolism*; D002522:Chlorocebus aethiops; D011992:Endosomes / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D054730:Protein Interaction Domains and Motifs; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011554:Pseudopodia / Q000378:metabolism / Q000502:physiology*; D058305:Sorting Nexins / Q000235:genetics / Q000378:metabolism*; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
D000199:Actins; D020662:Guanine Nucleotide Exchange Factors; C513978:SNX1 protein, human; C513979:SNX2 protein, human; D058305:Sorting Nexins; C075397:RHOG protein, human; C503866:KALRN protein, human; D017346:Protein Serine-Threonine Kinases; D020741:rho GTP-Binding Proteins