MKS and NPHP modules cooperate to establish basal body/transition zone membrane associations and ciliary gate function during ciliogenesis.
MKS and NPHP modules cooperate to establish basal body/transition zone membrane associations and ciliary gate function during ciliogenesis.
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MK和NPHP模块在纤毛发生过程中合作，建立基底体/过渡区膜关联和纤毛栅极功能。
DOI：
10.1083/jcb.201012116
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发表时间：
2011-03-21
期刊：
影响因子：
--
通讯作者：
Leroux MR
中科院分区：
文献类型：
--
作者：
Williams CL;Li C;Kida K;Inglis PN;Mohan S;Semenec L;Bialas NJ;Stupay RM;Chen N;Blacque OE;Yoder BK;Leroux MR
八种蛋白质，其中的缺陷与Meckel-Gruber综合征和肾单位痨纤毛病变，作为两个功能模块在过渡区一起工作，以建立基体/过渡区与膜的连接，并阻止非纤毛成分进入这个细胞器。Meckel-Gruber综合征（MKS）、肾单位营养不良（NPHP）和相关的纤毛病表现出重叠的表型，并在至少12个功能不明的不同基因之间显示出相当大的等位性。我们证明了保守的C. elegans B 9结构域（MKS-1、MKSR-1和MKSR-2）、MKS-3/TMEM 67、MKS-5/RPGRIP 1 L、MKS-6/CC 2D 2A、NPHP-1和NPHP-4蛋白在过渡区（TZ）表现出基本的集体功能，过渡区是所有纤毛基部的未被重视的区域，其特征在于将轴丝微管连接到周围膜的Y形集合体。这些TZ蛋白作为两个不同模块的成员在功能上相互作用，这两个模块共同促成了早期纤毛发生事件。具体而言，MKS/MKSR/NPHP蛋白建立基体/TZ膜附件之前或与鞭毛内转运依赖性轴丝延伸一致，随后限制纤毛室内的非纤毛成分的积累。总之，我们的研究结果揭示了一个统一的作用，为八个TZ-localized蛋白质在基体锚定和建立睫状门在纤毛发生，并表明，破坏睫状门功能有助于表型特征的MKS/NPHP疾病谱。
Eight proteins, defects in which are associated with Meckel-Gruber syndrome and nephronophthisis ciliopathies, work together as two functional modules at the transition zone to establish basal body/transition zone connections with the membrane and barricade entry of non-ciliary components into this organelle. Meckel-Gruber syndrome (MKS), nephronophthisis (NPHP), and related ciliopathies present with overlapping phenotypes and display considerable allelism between at least twelve different genes of largely unexplained function. We demonstrate that the conserved C. elegans B9 domain (MKS-1, MKSR-1, and MKSR-2), MKS-3/TMEM67, MKS-5/RPGRIP1L, MKS-6/CC2D2A, NPHP-1, and NPHP-4 proteins exhibit essential, collective functions at the transition zone (TZ), an underappreciated region at the base of all cilia characterized by Y-shaped assemblages that link axoneme microtubules to surrounding membrane. These TZ proteins functionally interact as members of two distinct modules, which together contribute to an early ciliogenic event. Specifically, MKS/MKSR/NPHP proteins establish basal body/TZ membrane attachments before or coinciding with intraflagellar transport–dependent axoneme extension and subsequently restrict accumulation of nonciliary components within the ciliary compartment. Together, our findings uncover a unified role for eight TZ-localized proteins in basal body anchoring and establishing a ciliary gate during ciliogenesis, and suggest that disrupting ciliary gate function contributes to phenotypic features of the MKS/NPHP disease spectrum.
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影响因子：
4.6
作者：
Bae, Young-Kyung;Qin, Hongmin;Barr, Maureen M.
通讯作者：
Barr, Maureen M.
影响因子：
--
作者：
HORST, CJ;JOHNSON, LV;BESHARSE, JC
通讯作者：
BESHARSE, JC
影响因子：
9.8
作者：
Gorden, Nicholas T.;Arts, Heleen H.;Doherty, Dan
通讯作者：
Doherty, Dan
DOI：
10.1002/ajmg.c.30231
发表时间：
2009-11-15
影响因子：
3.1
作者：
Baker, Kate;Beales, Philip L.
通讯作者：
Beales, Philip L.
影响因子：
4
作者：
Hao, Limin;Scholey, Jonathan M.
通讯作者：
Scholey, Jonathan M.