A hierarchy of signals regulates entry of membrane proteins into the ciliary membrane domain in epithelial cells.
A hierarchy of signals regulates entry of membrane proteins into the ciliary membrane domain in epithelial cells.
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DOI：
10.1083/jcb.201009001
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发表时间：
2011-04-04
期刊：
影响因子：
--
通讯作者：
Mellman I
中科院分区：
文献类型：
--
作者：
Francis SS;Sfakianos J;Lo B;Mellman I
NHERF 1-ERM-肌动蛋白网络包含一个选择性保留基质，可防止相互作用的膜蛋白进入睫状体膜。初级纤毛的膜与质膜是连续的，但成分不同。虽然一些膜蛋白集中在纤毛中，但其他蛋白如podocalyxin/gp 135被排除在外。我们发现，排斥反应反映了饱和的选择性保留机制。足糖萼蛋白通过其PDZ相互作用基序与NHERF 1结合而固定，从而通过ERM家族成员与顶端肌动蛋白网络结合。保留信号是占主导地位的，自主的，并转移到膜蛋白通常不排除纤毛。囊性纤维化跨膜传导调节因子和Csk结合蛋白的NHERF 1结合结构域也被发现作为可转移的保留信号。保留信号的添加可以抑制蛋白质的纤毛定位（例如，平滑的）含有通常促进纤毛膜中浓度的信号。没有保留信号的蛋白质（例如，绿色荧光蛋白-糖基磷脂酰肌醇），表明进入不受扩散屏障或脂质微区的阻碍。因此，相互作用的层次控制着睫状膜的组成，包括选择性保留、选择性包含和被动扩散。
The NHERF1-ERM-actin network comprises a selective retention matrix that prevents interacting membrane proteins from entering the ciliary membrane. The membrane of the primary cilium is continuous with the plasma membrane but compositionally distinct. Although some membrane proteins concentrate in the cilium, others such as podocalyxin/gp135 are excluded. We found that exclusion reflects a saturable selective retention mechanism. Podocalyxin is immobilized by its PDZ interaction motif binding to NHERF1 and thereby to the apical actin network via ERM family members. The retention signal was dominant, autonomous, and transferable to membrane proteins not normally excluded from the cilium. The NHERF1-binding domains of cystic fibrosis transmembrane conductance regulator and Csk-binding protein were also found to act as transferable retention signals. Addition of a retention signal could inhibit the ciliary localization of proteins (e.g., Smoothened) containing signals that normally facilitate concentration in the ciliary membrane. Proteins without a retention signal (e.g., green fluorescent protein–glycosylphosphatidylinositol) were found in the cilium, suggesting entry was not impeded by a diffusion barrier or lipid microdomain. Thus, a hierarchy of interactions controls the composition of the ciliary membrane, including selective retention, selective inclusion, and passive diffusion.
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DOI：
10.1083/jcb.200604046
发表时间：
2006-12-04
期刊：
The Journal of cell biology
影响因子：
--
作者：
Hanono A;Garbett D;Reczek D;Chambers DN;Bretscher A
通讯作者：
Bretscher A
影响因子：
11.8
作者：
Bershteyn, Marina;Atwood, Scott X.;Woo, Wei-Meng;Li, Mischa;Oro, Anthony E.
通讯作者：
Oro, Anthony E.
影响因子：
4
作者：
Geng, L;Okuhara, D;Somlo, S
通讯作者：
Somlo, S
DOI：
10.1152/ajprenal.00131.2001
发表时间：
2002-06-01
影响因子：
4.2
作者：
Li, Y;Li, J;Kershaw, DB
通讯作者：
Kershaw, DB
影响因子：
64.8
作者：
通讯作者：
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