Possible regulation of caveolar endocytosis and flattening by phosphorylation of F-BAR domain protein PACSIN2/Syndapin II.
Possible regulation of caveolar endocytosis and flattening by phosphorylation of F-BAR domain protein PACSIN2/Syndapin II.
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DOI：
10.1080/19490992.2015.1128604
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Suetsugu S
中科院分区：
文献类型：
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作者：
Senju Y;Suetsugu S
摘要。小窝是质膜的瓶状内陷。BAR结构域蛋白形成新月形的二聚体，并且它们的寡聚丝被认为在内陷的颈部形成螺旋，例如网格蛋白包被的凹坑和小窝。PACSIN 2/Syndapin II是一种含有BAR结构域的蛋白质，定位于小窝的颈部。认为PACSIN 2通过分别与发动蛋白-2和EHD 2结合，在小窝的断裂和稳定中起作用。这两种功能被认为是在低渗应激和剪切应激时通过蛋白激酶C（PKC）的PACSIN 2磷酸化来切换的。磷酸化降低了PACSIN 2的膜结合亲和力，导致其从小窝中去除。从小窝膜内陷中去除假定的PACSIN 2寡聚螺旋可能导致小窝变形。事实上，从小窝中去除PACSIN 2伴随着发动蛋白-2的募集，这表明去除为发动蛋白-2的功能提供了空间。另外，PACSIN 2的去除降低了小窝的稳定性，这可能导致小窝变平。相反，EHD 2的量的增加恢复小窝稳定性。因此，在小窝的PACSIN 2稳定小窝，但其通过磷酸化的去除可能会诱导小窝内吞和扁平化。
ABSTRACT. Caveolae are flask-shaped invaginations of the plasma membrane. The BAR domain proteins form crescent-shaped dimers, and their oligomeric filaments are considered to form spirals at the necks of invaginations, such as clathrin-coated pits and caveolae. PACSIN2/Syndapin II is one of the BAR domain-containing proteins, and is localized at the necks of caveolae. PACSIN2 is thought to function in the scission and stabilization of caveolae, through binding to dynamin-2 and EHD2, respectively. These two functions are considered to be switched by PACSIN2 phosphorylation by protein kinase C (PKC) upon hypotonic stress and sheer stress. The phosphorylation decreases the membrane binding affinity of PACSIN2, leading to its removal from caveolae. The removal of the putative oligomeric spiral of PACSIN2 from caveolar membrane invaginations could lead to the deformation of caveolae. Indeed, PACSIN2 removal from caveolae is accompanied by the recruitment of dynamin-2, suggesting that the removal provides space for the function of dynamin-2. Otherwise, the removal of PACSIN2 decreases the stability of caveolae, which could result in the flattening of caveolae. In contrast, an increase in the amount of EHD2 restored caveolar stability. Therefore, PACSIN2 at caveolae stabilizes caveolae, but its removal by phosphorylation could induce both caveolar endocytosis and flattening.