Centriolar association of ALMS1 and likely centrosomal functions of the ALMS motif-containing proteins C10orf90 and KIAA1731.
Centriolar association of ALMS1 and likely centrosomal functions of the ALMS motif-containing proteins C10orf90 and KIAA1731.
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DOI：
10.1091/mbc.e10-03-0246
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发表时间：
2010-11-01
影响因子：
3.3
通讯作者：
Hearn T
中科院分区：
文献类型：
--
作者：
Knorz VJ;Spalluto C;Lessard M;Purvis TL;Adigun FF;Collin GB;Hanley NA;Wilson DI;Hearn T
这项研究揭示了ALMS 1的亚中心体分布，ALMS 1是一种与初级纤毛形成和维持有关的人类蛋白质，并为其中心体相关功能提供了新的见解。还介绍了与ALMS 1共享C-末端序列相似性的两种人类蛋白质的第一个功能数据。人类基因ALMS 1的突变导致Alström综合征，这是一种罕见的进行性疾病，其特征是神经感觉变性和代谢缺陷。ALMS 1蛋白定位于中心体，并参与初级纤毛的组装和/或维持;然而，其确切的功能，在中心体内的分布，以及中心体募集的机制尚不清楚。ALMS 1的C-末端含有与未表征的人蛋白质C10 orf 90相似的区域，称为ALMS基序。在这里，我们表明，第三个人类蛋白质，候选中心体蛋白KIAA 1731，含有ALMS基序和外源表达KIAA 1731和C10 orf 90定位于中心体。然而，根据ALMS 1的缺失分析，ALMS基序似乎不太可能对中心体靶向至关重要。RNAi分析表明C10 orf 90和KIAA 1731分别在初级纤毛组装和中心粒形成/稳定中起作用。我们还表明，ALMS 1定位于特定的近端中心粒和基体，在那里它与中心体凝聚蛋白C-Nap 1共定位。RNAi分析显示，在ALMS 1缺失的细胞中，C-Nap 1的中心体水平显著降低，亲本中心粒的凝聚力受损。总之，这些数据表明C10 orf 90和KIAA 1731的中心体功能和ALMS 1的新的中心粒相关功能。
This study reveals the subcentrosomal distribution of ALMS1, a human protein implicated in primary cilium formation and maintenance, and provides new insight into its centrosome-related functions. The first functional data on two human proteins sharing C-terminal sequence similarity with ALMS1 are also presented. Mutations in the human gene ALMS1 cause Alström syndrome, a rare progressive condition characterized by neurosensory degeneration and metabolic defects. ALMS1 protein localizes to the centrosome and has been implicated in the assembly and/or maintenance of primary cilia; however its precise function, distribution within the centrosome, and mechanism of centrosomal recruitment are unknown. The C-terminus of ALMS1 contains a region with similarity to the uncharacterized human protein C10orf90, termed the ALMS motif. Here, we show that a third human protein, the candidate centrosomal protein KIAA1731, contains an ALMS motif and that exogenously expressed KIAA1731 and C10orf90 localize to the centrosome. However, based on deletion analysis of ALMS1, the ALMS motif appears unlikely to be critical for centrosomal targeting. RNAi analyses suggest that C10orf90 and KIAA1731 have roles in primary cilium assembly and centriole formation/stability, respectively. We also show that ALMS1 localizes specifically to the proximal ends of centrioles and basal bodies, where it colocalizes with the centrosome cohesion protein C-Nap1. RNAi analysis reveals markedly diminished centrosomal levels of C-Nap1 and compromised cohesion of parental centrioles in ALMS1-depleted cells. In summary, these data suggest centrosomal functions for C10orf90 and KIAA1731 and new centriole-related functions for ALMS1.