CRB3 binds directly to Par6 and regulates the morphogenesis of the tight junctions in mammalian epithelial cells
CRB3 binds directly to Par6 and regulates the morphogenesis of the tight junctions in mammalian epithelial cells
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DOI：
10.1091/mbc.e03-04-0235
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发表时间：
2004-03-01
影响因子：
3.3
通讯作者：
Le Bivic, A
中科院分区：
文献类型：
--
作者：
Lemmers, C;Michel, D;Le Bivic, A
Crumbs是果蝇胚胎上皮细胞形态发生的一种重要跨膜蛋白。已经从患有视网膜色素变性组12的患者中鉴定出具有Crumbs同源物的所有特征的蛋白质，但是这种蛋白质（CRB 1）仅在人和小鼠的视网膜和脑的某些部分中表达。在这里，我们描述CRB 3，另一种Crumbs同源物，优先在上皮组织和骨骼肌中表达。CRB 3与其他Crumbs共享保守的胞质结构域，但表现出非常短的胞外结构域，而没有其他Crumbs中存在的EGF和层粘连蛋白A样G重复。CRB 3定位于来自小鼠和人肠的上皮细胞的顶端和亚顶端区域，这表明它可以在上皮形态发生中发挥作用。事实上，CRB 3或含有神经营养因子受体p75 NTR的胞外结构域和CRB 3的跨膜和胞质结构域的嵌合体的表达导致Madin-Darby犬肾细胞中功能性紧密连接的发育较慢。这种表型依赖于CRB 3的最后四个氨基酸（ERLI）的存在，其参与与Par 6的直接相互作用，Par 6是上皮极性和紧密连接形成的调节剂。因此，CRB 3通过其胞质结构域及其相互作用物在顶膜形态发生和紧密连接调节中发挥作用。
Crumbs is an apical transmembrane protein crucial for epithelial morphogenesis in Drosophila melanogaster embryos. A protein with all the characteristics for a Crumbs homologue has been identified from patients suffering from retinitis pigmentosa group 12, but this protein (CRB1) is only expressed in retina and some parts of the brain, both in human and mouse. Here, we describe CRB3, another Crumbs homologue that is preferentially expressed in epithelial tissues and skeletal muscles in human. CRB3 shares the conserved cytoplasmic domain with other Crumbs but exhibits a very short extracellular domain without the EGF- and laminin A-like G repeats present in the other Crumbs. CRB3 is localized to the apical and subapical area of epithelial cells from the mouse and human intestine, suggesting that it could play a role in epithelial morphogenesis. Indeed, expression of CRB3 or of a chimera containing the extracellular domain of the neurotrophin receptor p75NTR and the transmembrane and cytoplasmic domains of CRB3 led to a slower development of functional tight junctions in Madin-Darby canine kidney cells. This phenotype relied on the presence of CRB3 four last amino acids (ERLI) that are involved in a direct interaction with Par6, a regulator of epithelial polarity and tight junction formation. Thus, CRB3, through its cytoplasmic domain and its interactors, plays a role in apical membrane morphogenesis and tight junction regulation.