Myosin VI is required for sorting of AP-1B-dependent cargo to the basolateral domain in polarized MDCK cells.
Myosin VI is required for sorting of AP-1B-dependent cargo to the basolateral domain in polarized MDCK cells.
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在极化MDCK细胞中，将肌球蛋白VI分选为基底外侧结构域的AP-1B依赖性货物。
DOI：
10.1083/jcb.200608126
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发表时间：
2007-04-09
影响因子：
7.8
通讯作者：
Buss, Folma
中科院分区：
文献类型：
--
作者：
Au, Josephine Sui-Yan;Puri, Claudia;Ihrke, Gudrun;Kendrick-Jones, John;Buss, Folma
在极化的上皮细胞中，根据蛋白质中存在的分类基序，新合成的膜蛋白通过特定的路径被运送到顶端或基侧区域。由于肌球蛋白VI已被证明促进非极化细胞的分泌运输，我们研究了它在极化MDCK细胞生物合成运输途径中的作用。我们观察到，含有基侧膜蛋白的酪氨酸基序的极化运输需要肌球蛋白VI的一个特定的剪接异构体，在尾部区域没有插入。然而，其他基侧或顶端货物的分选不涉及肌球蛋白VI。定点突变表明，由肌球蛋白VI、视神经磷酸酶和可能还有GTPase Rab8组成的功能复合体在膜蛋白的基侧递送中发挥作用，其分选是由网状蛋白适配器蛋白复合体(AP-1B)介导的。我们的结果表明，在极化上皮细胞中，肌球蛋白VI是AP-1B依赖的生物合成分选途径到基底外侧表面的关键成分。
In polarized epithelial cells, newly synthesized membrane proteins are delivered on specific pathways to either the apical or basolateral domains, depending on the sorting motifs present in these proteins. Because myosin VI has been shown to facilitate secretory traffic in nonpolarized cells, we investigated its role in biosynthetic trafficking pathways in polarized MDCK cells. We observed that a specific splice isoform of myosin VI with no insert in the tail domain is required for the polarized transport of tyrosine motif containing basolateral membrane proteins. Sorting of other basolateral or apical cargo, however, does not involve myosin VI. Site-directed mutagenesis indicates that a functional complex consisting of myosin VI, optineurin, and probably the GTPase Rab8 plays a role in the basolateral delivery of membrane proteins, whose sorting is mediated by the clathrin adaptor protein complex (AP) AP-1B. Our results suggest that myosin VI is a crucial component in the AP-1B–dependent biosynthetic sorting pathway to the basolateral surface in polarized epithelial cells.