TY - JOUR
T1 - SNX9 regulates tubular invagination of the plasma membrane through interaction with actin cytoskeleton and dynamin 2
AU - Shin, Narae
AU - Ahn, Namhui
AU - Chang-Ileto, Belle
AU - Park, Joohyun
AU - Takei, Kohji
AU - Ahn, Sang Gun
AU - Kim, Soo A.
AU - Di Paolo, Gilbert
AU - Chang, Sunghoe
PY - 2008/4/15
Y1 - 2008/4/15
N2 - Dynamic membrane remodeling during intracellular trafficking is controlled by the intricate interplay between lipids and proteins. BAR domains are modules that participate in endocytic processes by binding and deforming the lipid bilayer. Sorting nexin 9 (SNX9), which functions in clathrin-mediated endocytosis, contains a BAR domain, however, the properties of this domain are not well understood. Here we show that SNX9 shares many properties with other BAR domain-containing proteins, such as amphiphysin and endophilin. SNX9 is able to deform the plasma membrane, as well as liposomes, into narrow tubules and recruit N-WASP and dynamin 2 to these tubules via its SH3 domain. SNX9-induced tubulation is antagonized by N-WASP and dynamin 2 while it is enhanced by perturbation of actin dynamics. However, SNX9 also has several unique properties. The tubulating activity requires the BAR and PX domains, as well as the low-complexity (LC) domain, which binds the Arp2/3 complex. SNX9 also binds to PtdIns(4)P-5-kinases via its PX domain and its tubulating activity is regulated by phosphoinositides. In addition, the kinase activity of PtdIns(4)P-5-kinases is stimulated by interaction with SNX9, suggesting a positive feedback interaction between SNX9 and PtdIns(4)P-5-kinases. These results suggest that SNX9 functions in the coordination of membrane remodeling and fission via interactions with actin-regulating proteins, endocytic proteins and PtdIns(4,5)P2-metabolizing enzymes.
AB - Dynamic membrane remodeling during intracellular trafficking is controlled by the intricate interplay between lipids and proteins. BAR domains are modules that participate in endocytic processes by binding and deforming the lipid bilayer. Sorting nexin 9 (SNX9), which functions in clathrin-mediated endocytosis, contains a BAR domain, however, the properties of this domain are not well understood. Here we show that SNX9 shares many properties with other BAR domain-containing proteins, such as amphiphysin and endophilin. SNX9 is able to deform the plasma membrane, as well as liposomes, into narrow tubules and recruit N-WASP and dynamin 2 to these tubules via its SH3 domain. SNX9-induced tubulation is antagonized by N-WASP and dynamin 2 while it is enhanced by perturbation of actin dynamics. However, SNX9 also has several unique properties. The tubulating activity requires the BAR and PX domains, as well as the low-complexity (LC) domain, which binds the Arp2/3 complex. SNX9 also binds to PtdIns(4)P-5-kinases via its PX domain and its tubulating activity is regulated by phosphoinositides. In addition, the kinase activity of PtdIns(4)P-5-kinases is stimulated by interaction with SNX9, suggesting a positive feedback interaction between SNX9 and PtdIns(4)P-5-kinases. These results suggest that SNX9 functions in the coordination of membrane remodeling and fission via interactions with actin-regulating proteins, endocytic proteins and PtdIns(4,5)P2-metabolizing enzymes.
KW - Actin cytoskeleton
KW - Bin-Amphiphysin-Rvs (BAR)
KW - Clathrin-mediated endocytosis
KW - Dynamin
KW - Membrane tubulation
KW - Neural Wiskott-Aldrich syndrome protein (N-WASP)
KW - Sorting nexin 9 (SNX9)
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U2 - 10.1242/jcs.016709
DO - 10.1242/jcs.016709
M3 - Article
C2 - 18388313
AN - SCOPUS:44449169861
SN - 0021-9533
VL - 121
SP - 1252
EP - 1263
JO - The Quarterly journal of microscopical science
JF - The Quarterly journal of microscopical science
IS - 8
ER -