The WD40 protein Morg1 facilitates Par6-aPKC binding to Crb3 for apical identity in epithelial cells.
The WD40 protein Morg1 facilitates Par6-aPKC binding to Crb3 for apical identity in epithelial cells.
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DOI：
10.1083/jcb.201208150
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发表时间：
2013-03-04
期刊：
影响因子：
--
通讯作者：
Sumimoto H
中科院分区：
文献类型：
--
作者：
Hayase J;Kamakura S;Iwakiri Y;Yamaguchi Y;Izaki T;Ito T;Sumimoto H
Par 6-aPKC通过Morg 1与Par 6的相互作用募集到过早的顶端膜是定义上皮细胞顶端身份所必需的。上皮细胞中顶-底极性的形成对于形态发生（例如，囊肿形成）和功能（例如，紧密连接发展）。与Par 6复合的非典型蛋白激酶C（aPKC）被认为移位至顶端膜并在上皮细胞极化中起作用。然而，Par 6-aPKC复合物的易位机制在很大程度上仍然未知。在这里，我们表明，WD 40蛋白Morg 1（丝裂原活化蛋白激酶组织者1）直接结合到Par 6，从而促进顶端靶向的Par 6-aPKC在Madin-Darby犬肾上皮细胞。Morg 1还与顶端跨膜蛋白Crumbs 3相互作用，以促进Par 6-aPKC与Crumbs 3的结合，这是由顶端定位的小GTdc 42加强的。Morg 1的耗竭破坏了单层培养中的紧密连接发育和三维培养中的囊肿形成;通过强制aPKC靶向至顶端表面，顶端-基底极性显著恢复。因此，Par 6-aPKC募集到过早的顶端膜似乎是定义上皮细胞的顶端身份所必需的。
Par6–aPKC recruitment to the premature apical membrane through Morg1 interaction with Par6 is required for definition of apical identity of epithelial cells. Formation of apico-basal polarity in epithelial cells is crucial for both morphogenesis (e.g., cyst formation) and function (e.g., tight junction development). Atypical protein kinase C (aPKC), complexed with Par6, is considered to translocate to the apical membrane and function in epithelial cell polarization. However, the mechanism for translocation of the Par6–aPKC complex has remained largely unknown. Here, we show that the WD40 protein Morg1 (mitogen-activated protein kinase organizer 1) directly binds to Par6 and thus facilitates apical targeting of Par6–aPKC in Madin-Darby canine kidney epithelial cells. Morg1 also interacts with the apical transmembrane protein Crumbs3 to promote Par6–aPKC binding to Crumbs3, which is reinforced with the apically localized small GTPase Cdc42. Depletion of Morg1 disrupted both tight junction development in monolayer culture and cyst formation in three-dimensional culture; apico-basal polarity was notably restored by forced targeting of aPKC to the apical surface. Thus, Par6–aPKC recruitment to the premature apical membrane appears to be required for definition of apical identity of epithelial cells.
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影响因子：
4
作者：
Ferrari, Aldo;Veligodskiy, Alexey;Kroschewski, Ruth
通讯作者：
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影响因子：
3.3
作者：
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通讯作者：
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影响因子：
64.8
作者：
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Knoblich, JA
影响因子：
2.1
作者：
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通讯作者：
Takeichi, Masatoshi
DOI：
10.1152/ajprenal.00204.2009
发表时间：
2009-11-01
影响因子：
4.2
作者：
Hammerschmidt, Elke;Loeffler, Ivone;Wolf, Gunter
通讯作者：
Wolf, Gunter