CAMDI, a Novel Disrupted in Schizophrenia 1 (DISC1)-binding Protein, Is Required for Radial Migration
CAMDI, a Novel Disrupted in Schizophrenia 1 (DISC1)-binding Protein, Is Required for Radial Migration
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DOI：
10.1074/jbc.m110.179481
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发表时间：
2010-12-24
影响因子：
4.8
通讯作者：
Yanagi, Shigeru
中科院分区：
文献类型：
--
作者：
Fukuda, Toshifumi;Sugita, Satoko;Yanagi, Shigeru
中心体在发育中神经元的定向迁移中起着至关重要的作用。然而，人们对其潜在机制知之甚少。本研究发现了一种新的在精神分裂症1(DISC1)中被破坏的相互作用蛋白，命名为CAMDI，与肌球蛋白II和DISC1相关的卷曲蛋白以DISC1依赖的方式移位到中心体。通过shRNA敲除CAMDI，发现中心体失定向的径向迁移严重受损。酵母双杂交鉴定肌球蛋白II为CAMDI结合蛋白。CAMDI优先与磷化肌球蛋白II相互作用，并以依赖于DISC1的方式在中心体诱导磷化肌球蛋白II的积聚。有趣的是，CAMDI基因的一个单核苷酸多态(R828W)被发现，其基因产物降低了与磷酸肌球蛋白II的结合能力。此外，R828W在神经元中过表达的小鼠表现出径向迁移障碍。我们的发现表明，在神经元发育过程中，可能通过DISC1和肌球蛋白II介导的中心体定位，CAMDI是径向迁移所必需的。
Centrosomes play a crucial role in the directed migration of developing neurons. However, the underlying mechanism is poorly understood. This study has identified a novel disrupted in schizophrenia 1 (DISC1)-interacting protein, named CAMDI after coiled-coil protein associated with myosin II and DISC1, which translocates to the centrosome in a DISC1-dependent manner. Knockdown of CAMDI by shRNA revealed severely impaired radial migration with disoriented centrosomes. A yeast two-hybrid screen identified myosin II as a binding protein of CAMDI. CAMDI interacts preferentially with phosphomyosin II and induces an accumulation of phosphomyosin II at the centrosome in a DISC1-dependent manner. Interestingly, one single nucleotide polymorphism of the CAMDI gene (R828W) is identified, and its gene product was found to reduce the binding ability to phosphomyosin II. Furthermore, mice with overexpression of R828W in neurons exhibit an impaired radial migration. Our findings indicate that CAMDI is required for radial migration probably through DISC1 and myosin II-mediated centrosome positioning during neuronal development.