[PDF][PDF] SNX9 couples actin assembly to phosphoinositide signals and is required for membrane remodeling during endocytosis

D Yarar, CM Waterman-Storer, SL Schmid - Developmental cell, 2007 - cell.com
Developmental cell, 2007cell.com
Multiple modes of endocytosis require actin-dependent remodeling of the plasma
membrane; however, neither the factors linking these processes nor their mechanisms of
action are understood. The sorting nexin, SNX9, localizes to clathrin-coated pits where it
interacts with dynamin and functions in clathrin-mediated endocytosis. Here, we
demonstrate that SNX9 also localizes to actin-rich structures implicated in fluid-phase
uptake, including tubular membranes containing GPI-anchored proteins and dorsal …
Summary
Multiple modes of endocytosis require actin-dependent remodeling of the plasma membrane; however, neither the factors linking these processes nor their mechanisms of action are understood. The sorting nexin, SNX9, localizes to clathrin-coated pits where it interacts with dynamin and functions in clathrin-mediated endocytosis. Here, we demonstrate that SNX9 also localizes to actin-rich structures implicated in fluid-phase uptake, including tubular membranes containing GPI-anchored proteins and dorsal membrane ruffles. Moreover, we show that SNX9 is critical for dorsal ruffle formation and for clathrin-independent, actin-dependent fluid-phase endocytosis. In vitro, SNX9 directly associates with N-WASP, an Arp2/3 complex activator, and stimulates N-WASP/Arp2/3-mediated actin assembly. SNX9-stimulated actin polymerization is greatly enhanced by PI4,5P2-containing liposomes, due in part to PI4,5P2-induced SNX9 oligomerization. These results suggest a mechanism for the spatial and temporal regulation of N-WASP-dependent actin assembly and implicate SNX9 in directly coupling actin dynamics to membrane remodeling during multiple modes of endocytosis.
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