Picower Institute for Learning and Memory, Department of Brain and Cognitive, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Building 46, Room 4235A, Cambridge, MA 02139, USA.
Neuron. 2010 Jan 28;65(2):191-203. doi: 10.1016/j.neuron.2010.01.011.
Centrosome functions are important in multiple brain developmental processes. Proper functioning of the centrosome relies on assembly of protein components into the pericentriolar material. This dynamic assembly is mediated by the trafficking of pericentriolar satellites, which are comprised of centrosomal proteins. Here we demonstrate that trafficking of pericentriolar satellites requires the interaction between Hook3 and Pericentriolar Material 1 (PCM1). Hook3, previously shown to link the centrosome and the nucleus in C. elegans, is recruited to pericentriolar satellites through interaction with PCM1, a protein associated with schizophrenia. Disruption of the Hook3-PCM1 interaction in vivo impairs interkinetic nuclear migration, a featured behavior of embryonic neural progenitors. This in turn leads to overproduction of neurons and premature depletion of the neural progenitor pool in the developing neocortex. These results underscore the importance of centrosomal assembly in neurogenesis and provide potential insights into the etiology of brain developmental diseases related to the centrosome dysfunction.
中心体的功能在多种脑发育过程中很重要。中心体的正常功能依赖于蛋白质组件组装成中心粒周围物质。这种动态组装是由中心粒卫星的运输介导的，中心粒卫星由中心体蛋白组成。在这里，我们证明了中心粒卫星的运输需要 Hook3 和 Pericentriolar 材料 1（PCM1）之间的相互作用。Hook3 以前在秀丽隐杆线虫中被证明可以将中心体和细胞核连接起来，它通过与 PCM1（一种与精神分裂症相关的蛋白质）相互作用被招募到中心粒卫星中。体内破坏 Hook3-PCM1 相互作用会损害核动力学迁移，这是胚胎神经祖细胞的一个特征行为。这反过来又导致神经元过度产生和发育中的新皮质神经祖细胞池过早耗尽。这些结果强调了中心体组装在神经发生中的重要性，并为与中心体功能障碍相关的脑发育疾病的病因提供了潜在的见解。
