TY - JOUR
T1 - SNX9 Couples Actin Assembly to Phosphoinositide Signals and Is Required for Membrane Remodeling during Endocytosis
AU - Yarar, Defne
AU - Waterman-Storer, Clare M.
AU - Schmid, Sandra L.
N1 - Funding Information:
We are especially grateful to E. Goley for the insect cell pellet containing rArp2/3 complex. We also thank C. Co and J. Taunton for ΔEVH1 N-WASP DNA; B. Qualmann and M. Kessels for syndapin II cDNA; J. Chappie for rabbit muscle myosin II; J. Lippincott-Schwartz for GFP-GPI plasmid; T. Kirchhausen for cells; B. Shin for maintenance of microscopes; I. Cheeseman, A. Maddox, T. Pucadyil, M. Surka, M. Leonard, and N. Alto for comments on the manuscript; and I. Cheeseman and members of the Schmid lab for thoughtful discussions. This work was supported by NIH grants GM31645, GM42455, and MH61345 to S.L.S., NIH grant GM67230 to C.W.S., and ACS Fellowship PF-04-105-01-CSM and LLS fellowship 3432-07 to D.Y. This is TSRI Manuscript No. 18471.
PY - 2007/7/3
Y1 - 2007/7/3
N2 - 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.
AB - 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.
KW - CELLBIO
UR - http://www.scopus.com/inward/record.url?scp=34250844333&partnerID=8YFLogxK
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U2 - 10.1016/j.devcel.2007.04.014
DO - 10.1016/j.devcel.2007.04.014
M3 - Article
C2 - 17609109
AN - SCOPUS:34250844333
SN - 1534-5807
VL - 13
SP - 43
EP - 56
JO - Developmental cell
JF - Developmental cell
IS - 1
ER -