SH3YL1 regulates dorsal ruffle formation by a novel phosphoinositide-binding domain

被引：71

作者：

Hasegawa, Junya ^{[1
]}

Tokuda, Emi ^{[2
]}

Tenno, Takeshi ^{[3
]}

Tsujita, Kazuya ^{[2
]}

Sawai, Haruko ^{[1
]}

Hiroaki, Hidekazu ^{[3
]}

Takenawa, Tadaomi ^{[2
]}

Itoh, Toshiki ^{[1
]}

机构：

[1] Kobe Univ, Grad Sch Med, Div Membrane Biol, Dept Biochem & Mol Biol, Kobe, Hyogo 6500017, Japan

[2] Kobe Univ, Grad Sch Med, Div Lipid Biochem, Dept Biochem & Mol Biol, Kobe, Hyogo 6500017, Japan

[3] Kobe Univ, Grad Sch Med, Div Struct Biol, Dept Biochem & Mol Biol, Kobe, Hyogo 6500017, Japan

来源：

JOURNAL OF CELL BIOLOGY | 2011年 / 193卷 / 05期

基金：

日本学术振兴会;

关键词：

MEMBRANE CURVATURE; ACTIN CYTOSKELETON; GROWTH-FACTOR; PODOSOME FORMATION; PLASMA-MEMBRANE; CELL-MIGRATION; BAR DOMAINS; ENDOCYTOSIS; DYNAMIN; MACROPINOCYTOSIS;

D O I：

10.1083/jcb.201012161

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Reversible interactions between cytosolic proteins and membrane lipids such as phosphoinositides play important roles in membrane morphogenesis driven by actin polymerization. In this paper, we identify a novel lipid-binding module, which we call the SYLF domain (after the SH3YL1, Ysc84p/Lsb4p, Lsb3p, and plant FYVE proteins that contain it), that is highly conserved from bacteria to mammals. SH3YL1 (SH3 domain containing Ysc84-like 1) strongly bound to phosphatidyl-inositol 3,4,5-triphosphate (PI(3,4,5)P(3)) and several D5-phosphorylated phosphoinositides through its SYLF domain and was localized to circular dorsal ruffles induced by platelet-derived growth factor stimulation. Interestingly, SHIP2 (the PI(3,4,5)P(3) 5-phosphatase, src-homology 2-containing inositol-5-phosphatase 2) was identified as a binding partner of SH3YL1, and knockdown of these proteins significantly suppressed dorsal ruffle formation. Phosphatidylinositol 3,4-bisphosphate (PI(3,4)P(2)), which is mainly synthesized from PI(3,4,5)P(3) by the action of SHIP2, was enriched in dorsal ruffles, and PI(3,4)P(2) synthesis strongly correlated with formation of the circular membrane structure. These results provide new insight into the molecular mechanism of dorsal ruffle formation and its regulation by phosphoinositide metabolism.

引用

页码：901 / 916

页数：16

共 53 条

[1] A novel mouse gene, Sh3yl1, is expressed in the anagen hair follicle [J].