Selective control of basolateral membrane protein polarity by cdc42
Selective control of basolateral membrane protein polarity by cdc42
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DOI：
10.1034/j.1600-0854.2001.20805.x
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发表时间：
2001-08-01
期刊：
影响因子：
4.5
通讯作者：
Rodriguez-Boulan, E
中科院分区：
文献类型：
--
作者：
Cohen, D;Müsch, A;Rodriguez-Boulan, E
Rho GTP酶cdc42与细胞极性的多个方面有关。最近的一项研究（Kroschewski R，Hall A，Mellman I.《自然细胞生物学》1999年；1：8 - 13）表明，cdc42的一种显性负性突变体消除了MDCK细胞中基底外侧膜蛋白的极性，但没有阐明这种效应是对基底外侧蛋白具有选择性，还是对所有分泌蛋白都无选择性。为了回答这个问题，我们分析了先前被诱导过表达cdc42突变形式的MDCK细胞系中新生合成的膜蛋白和可溶性蛋白的极性。GTP酶缺陷型和显性负性的cdc42不影响一种新生合成的顶端膜蛋白向顶端的靶向运输，但使两种外源性基底外侧膜蛋白的分布反转至顶端。与之形成鲜明对比的是，GTP酶缺陷型的cdc42不影响内源性可溶性蛋白（无论是顶端的还是基底外侧的）的极化胞吐作用。cdc42对极化蛋白靶向的精细选择性调节可能使细胞在发育、迁移以及对损伤作出反应时，能够根据细胞外信号微调其膜成分。
The rho GTPase cdc42 is implicated in several aspects of cell polarity. A recent study (Kroschewski R, Hall A, Mellman I. Nat Cell Biol 1999;1:8-13) demonstrated that a dominant negative mutant of cdc42 abolishes the polarity of basolateral membrane proteins in MDCK cells, but did not elucidate whether this effect was selective for basolateral proteins or nonselective for all secreted proteins. To answer this question, we analyzed the polarity of newly synthesized membrane and soluble proteins in MDCK cell lines previously induced to overexpress mutant forms of cdc42. GTPase-deficient and dominant negative cdc42 did not affect the apical targeting of a newly synthesized apical membrane protein, but reversed to apical the distribution of two exogenous basolateral membrane proteins. In striking contrast, GTPase-deficient cdc42 did not affect polarized exocytosis of endogenous soluble proteins, either apical or basolateral. The exquisitely selective regulation of polarized protein targeting by cdc42 may allow cells to fine-tune their membrane composition in response to extracellular signals during development, migration and in response to injury.