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原发性纤毛形成和纤毛蛋白转运受人和细胞中非典型 MAP 激酶 MAPK15 的调控。

Primary Cilium Formation and Ciliary Protein Trafficking Is Regulated by the Atypical MAP Kinase MAPK15 in and Human Cells.

机构信息

Department of Biology, Brandeis University, Waltham, Massachusetts 02454.

National Center for Behavioral Genomics, Brandeis University, Waltham, Massachusetts 02454.

出版信息

Genetics. 2017 Dec;207(4):1423-1440. doi: 10.1534/genetics.117.300383. Epub 2017 Oct 11.

Abstract

Motile and immotile (or primary) cilia are microtubule-based structures that mediate multiple cellular functions, including the transduction of environmental cues, developmental signaling, cellular motility, and modulation of fluid flow. Although their core architectures are similar, motile and primary cilia exhibit marked structural differences that underlie distinct functional properties. However, the extent to which ciliogenesis mechanisms are shared between these different cilia types is not fully described. Here, we report that the atypical MAP kinase MAPK15 (ERK7/8), implicated in the formation of vertebrate motile cilia, also regulates the formation of primary cilia in sensory neurons and human cells. We find that MAPK15 localizes to a basal body subdomain with the ciliopathy protein BBS7 and to cell-cell junctions. MAPK15 also regulates the localization of ciliary proteins involved in cilium structure, transport, and signaling. Our results describe a primary cilia-related role for this poorly studied member of the MAPK family , and indicate a broad requirement for MAPK15 in the formation of multiple ciliary classes across species.

摘要

能动和非能动(或初级)纤毛是基于微管的结构,介导多种细胞功能,包括环境线索的转导、发育信号、细胞运动和流体流动的调节。虽然它们的核心结构相似,但能动和初级纤毛表现出明显的结构差异,这是其不同功能特性的基础。然而,这些不同类型的纤毛之间的纤毛发生机制在何种程度上是共享的,目前还不完全清楚。在这里,我们报告说,参与脊椎动物能动纤毛形成的非典型 MAP 激酶 MAPK15(ERK7/8),也调节感觉神经元和人细胞中初级纤毛的形成。我们发现 MAPK15 定位于与纤毛病蛋白 BBS7 相关的基底体亚区和细胞-细胞连接处。MAPK15 还调节参与纤毛结构、运输和信号转导的纤毛蛋白的定位。我们的结果描述了这个 MAPK 家族中研究甚少的成员在初级纤毛中的一个相关作用,并表明 MAPK15 在跨物种的多种纤毛类别的形成中具有广泛的需求。

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