Modulating signaling events in smooth muscle: cleavage of annexin 2 abolishes its binding to lipid rafts
Modulating signaling events in smooth muscle: cleavage of annexin 2 abolishes its binding to lipid rafts
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DOI：
10.1096/fj.02-0070com
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发表时间：
2002-08-01
期刊：
影响因子：
4.8
通讯作者：
Draeger, A
中科院分区：
文献类型：
--
作者：
Babiychuk, EB;Monastyrskaya, K;Draeger, A
细胞膜区隔化被认为涉及富含胆固醇和糖鞘脂的膜筏的关联，是跨质膜传递信息的重要手段。我们之前已经表明筏关联是由Ca2+依赖的膜联蛋白2结合到质膜介导的。在本研究中，我们证明了膜联蛋白1和2与平滑肌细胞膜的结合可以通过它们的蛋白水解裂解而终止。这种蛋白水解被认为是由钙蛋白酶引发的，发生在质膜的非筏区。它严重依赖于细胞内游离Ca2+的浓度，需要一个完整的收缩装置。膜联蛋白1和2与不同的膜微室相互作用，前者与非筏状甘油脂区相互作用，后者优先与膜筏相互作用。我们证明PKC和RhoA是调节平滑肌收缩的主要信号分子，它们在空间上是分离的，并与不同的膜微室相互作用。蛋白水解会消除膜联蛋白与质膜的结合，并可能导致膜成分的重排，随后是分离依赖的信号事件的中断。
Cell membrane compartmentalization, which is believed to involve association of cholesterol- and glycosphingolipid-enriched membrane rafts, represents an important means of transmitting information across the plasma membrane. We have previously shown that raft association is mediated by the Ca2+ dependent binding of annexin 2 to the plasma membrane. In the present study, we demonstrate that the association of annexins 1 and 2 with the smooth muscle cell membrane can be terminated by their proteolytic cleavage. This proteolysis is thought to be triggered by calpain and occurs at non-raft regions of the plasma membrane. It is critically dependent on the intracellular concentration of free Ca2+ and requires an intact contractile apparatus. Annexins 1 and 2 interact with different membrane microcompartments-the former with non-raft, glycerolipid regions, the latter preferentially with membrane rafts. We demonstrate that PKC and RhoA, major signaling molecules that regulate smooth muscle contraction, are spatially segregated and interact with distinct membrane microcompartments. Proteolysis abolishes annexin binding to the plasma membrane and might result in rearrangement of membrane constituents followed by the interruption of segregation-dependent signaling events.