SH3YL1 regulates dorsal ruffle formation by a novel phosphoinositide-binding domain
SH3YL1 regulates dorsal ruffle formation by a novel phosphoinositide-binding domain
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DOI：
10.1083/jcb.201012161
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发表时间：
2011-05-30
影响因子：
7.8
通讯作者：
Itoh, Toshiki
中科院分区：
文献类型：
--
作者：
Hasegawa, Junya;Tokuda, Emi;Itoh, Toshiki
胞质蛋白和膜脂质（例如磷酸肌醇）之间的可逆相互作用在肌动蛋白聚合驱动的膜形态发生中发挥重要作用。在本文中，我们鉴定了一种新型脂质结合模块，我们将其称为 SYLF 结构域（以含有该结构域的 SH3YL1、Ysc84p/Lsb4p、Lsb3p 和植物 FYVE 蛋白命名），该模块从细菌到哺乳动物都高度保守。 SH3YL1（包含 Ysc84 样 1 的 SH3 结构域）通过其 SYLF 结构域与磷脂酰肌醇 3,4,5-三磷酸 (PI(3,4,5)P(3)) 和几种 D5 磷酸化磷酸肌醇强烈结合，并定位于由血小板源性生长因子刺激诱导的圆形背侧皱褶。有趣的是，SHIP2（PI(3,4,5)P(3) 5-磷酸酶，含有 src-homology 2 的肌醇-5-磷酸酶 2）被鉴定为 SH3YL1 的结合伴侣，并且这些蛋白质的敲低显着抑制了背侧皱褶的形成。磷脂酰肌醇3,4-二磷酸(PI(3,4)P(2))主要由PI(3,4,5)P(3)通过SHIP2的作用合成，在背侧皱褶中富集，PI(3,4)P(2)的合成与圆形膜结构的形成密切相关。这些结果为背侧皱褶形成的分子机制及其通过磷酸肌醇代谢的调节提供了新的见解。
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.