Trans-endocytosis of CD47 and SHPS-1 and its role in regulation of the CD47-SHPS-1 system
Trans-endocytosis of CD47 and SHPS-1 and its role in regulation of the CD47-SHPS-1 system
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DOI：
10.1242/jcs.025015
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发表时间：
2008-04-15
影响因子：
4
通讯作者：
Matozaki, Takashi
中科院分区：
文献类型：
--
作者：
Kusakari, Shinya;Ohnishi, Hiroshi;Matozaki, Takashi
CD47和SHPS-1是跨膜蛋白，它们通过细胞外区域相互作用，构成双向细胞间通讯系统（CD47-SHPS-1系统）。我们现在已经证明，表达 CD47 的 CHO 细胞和表达 SHPS-1 的 CHO 细胞接触时发生的 CD47 和 SHPS-1 的反式相互作用导致配体-受体复合物内吞到任一细胞类型中。发现表达 SHPS-1 的细胞对 CD47 的这种转内吞作用是由网格蛋白和动力介导的。 SHPS-1 的近膜区域对于 CD47 的有效反式内吞作用是必不可少的，CD47 也受到 Rac 和 Cdc42 的调节，可能是通过肌动蛋白细胞骨架的重组来调节。 CD47反式内吞作用的抑制促进了表达CD47的细胞与表达SHPS-1的细胞的聚集。此外，培养的小鼠海马神经元表面表达的 CD47 被表达内源性 SHPS-1 的邻近星形胶质细胞进行反式内吞作用。这些结果表明，CD47 的反式内吞作用负责从细胞表面去除 CD47-SHPS-1 复合物，从而调节 CD47-SHPS-1 系统的功能，至少在神经元和神经胶质细胞中是如此。
CD47 and SHPS-1 are transmembrane proteins that interact with each other through their extracellular regions and constitute a bidirectional cell-cell communication system (the CD47-SHPS-1 system). We have now shown that the trans-interaction of CD47 and SHPS-1 that occurred on contact of CD47-expressing CHO cells and SHPS-1-expressing CHO cells resulted in endocytosis of the ligand-receptor complex into either cell type. Such trans-endocytosis of CD47 by SHPS-1-expressing cells was found to be mediated by clathrin and dynamin. A juxtamembrane region of SHPS-1 was indispensable for efficient trans-endocytosis of CD47, which was also regulated by Rac and Cdc42, probably through reorganization of the actin cytoskeleton. Inhibition of trans-endocytosis of CD47 promoted the aggregation of CD47-expressing cells with the cells expressing SHPS-1. Moreover, CD47 expressed on the surface of cultured mouse hippocampal neurons was shown to undergo trans-endocytosis by neighboring astrocytes expressing endogenous SHPS-1. These results suggest that trans-endocytosis of CD47 is responsible for removal of the CD47-SHPS-1 complex from the cell surface and hence regulates the function of the CD47-SHPS-1 system, at least in neurons and glial cells.