Missing-in-metastasis and IRSp53 deform PI(4,5)P2-rich membranes by an inverse BAR domain-like mechanism.
Missing-in-metastasis and IRSp53 deform PI(4,5)P2-rich membranes by an inverse BAR domain-like mechanism.
复制标题
毫秒内丢失的 - irsp53变形PI（4,5）富含p2的膜通过类似bar域的机制。
DOI：
10.1083/jcb.200609176
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发表时间：
2007-03-26
影响因子：
7.8
通讯作者：
Lappalainen, Pekka
中科院分区：
文献类型：
--
作者：
Mattila, Pieta K;Pykalainen, Anette;Saarikangas, Juha;Paavilainen, Ville O;Vihinen, Helena;Jokitalo, Eija;Lappalainen, Pekka
肌动蛋白细胞骨架在涉及膜动力学的各种运动和形态发生过程中起着重要作用。我们发现肌动蛋白结合蛋白MIM （missing-in-metastasis）和IRSp53直接结合富含PI(4,5) p2的膜并使其变形为管状结构。这种活性存在于这些蛋白的n端IRSp53/MIM结构域（IMD）中，该结构域在结构上与膜管BAR （Bin/amphiphysin/Rvs）结构域相关。我们发现，由于PI(4,5) p2结合位点的几何形状不同，IMDs诱导与BAR结构域相反的膜曲率，并通过结合到小管内部使膜变形。这解释了为什么IMD蛋白诱导质膜突出而不是内陷。我们还提供证据表明，IMDs的膜变形活性，而不是先前提出的f -actin捆绑或gtpase结合活性，是诱导培养的哺乳动物细胞丝状足/微尖刺的关键。总之，这些数据揭示了肌动蛋白动力学和一种新的膜变形活性之间的相互作用促进了细胞的运动和形态发生。
The actin cytoskeleton plays a fundamental role in various motile and morphogenetic processes involving membrane dynamics. We show that actin-binding proteins MIM (missing-in-metastasis) and IRSp53 directly bind PI(4,5)P2-rich membranes and deform them into tubular structures. This activity resides in the N-terminal IRSp53/MIM domain (IMD) of these proteins, which is structurally related to membrane-tubulating BAR (Bin/amphiphysin/Rvs) domains. We found that because of a difference in the geometry of the PI(4,5)P2-binding site, IMDs induce a membrane curvature opposite that of BAR domains and deform membranes by binding to the interior of the tubule. This explains why IMD proteins induce plasma membrane protrusions rather than invaginations. We also provide evidence that the membrane-deforming activity of IMDs, instead of the previously proposed F-actin–bundling or GTPase-binding activities, is critical for the induction of the filopodia/microspikes in cultured mammalian cells. Together, these data reveal that interplay between actin dynamics and a novel membrane-deformation activity promotes cell motility and morphogenesis.