Abstract：
Caveolae are small plasma membrane invaginations, important for control of membrane tension, signaling cascades, and lipid sorting. The caveola coat protein Cavin1 is essential for shaping such high curvature membrane structures. Yet, a mechanistic understanding of how Cavin1 assembles at the membrane interface is lacking. Here, we used model membranes combined with biophysical dissection and computational modeling to show that Cavin1 inserts into membranes. We establish that initial phosphatidylinositol (4, 5) bisphosphate [PI(4,5)P2]-dependent membrane adsorption of the trimeric helical region 1 (HR1) of Cavin1 mediates the subsequent partial separation and membrane insertion of the individual helices. Insertion kinetics of HR1 is further enhanced by the presence of flanking negatively charged disordered regions, which was found important for the coassembly of Cavin1 with Caveolin1 in living cells. We propose that this intricate mechanism potentiates membrane curvature generation and facilitates dynamic rounds of assembly and disassembly of Cavin1 at the membrane.
摘要：
小窝是小的质膜内陷，对于膜张力的控制很重要，信令级联，和脂质分选。caveola外壳蛋白Cavin1对于塑造这种高曲率膜结构至关重要。然而，缺乏对Cavin1如何在膜界面组装的机械理解。这里,我们使用模型膜结合生物物理解剖和计算模型来显示Cavin1插入到膜中。我们确定，Cavin1的三聚体螺旋区1（HR1）的初始磷脂酰肌醇（4，5）二磷酸[PI（4，5）P2]依赖性膜吸附介导了随后的部分分离和单个螺旋的膜插入。侧翼带负电荷的无序区域的存在进一步增强了HR1的插入动力学，这对于活细胞中Cavin1与Caveolin1的共组装很重要。我们建议这种复杂的机制增强了膜曲率的产生，并促进了Cavin1在膜上的动态组装和拆卸。
