Paramasivam Murugan, Chang Yoon Jeung, LoTurco Joseph J
Department of Physiology and Neurobiology, University of Connecticut, Storrs, Connecticut 06269, USA.
Cell Cycle. 2007 Jul 1;6(13):1605-12. doi: 10.4161/cc.6.13.4356. Epub 2007 Apr 27.
Mutations in ASPM (abnormal spindle-like microcephaly associated) and citron kinase (CITK) cause primary microcephaly in humans and rodents, respectively. Both proteins are expressed during neurogenesis and play important roles in neuronal progenitor cell division. ASPM is localized to the spindle pole, and is essential for maintaining proliferative cell division. CITK is present at the cytokinesis furrow and midbody ring, and it is essential for cellular abscission. We report here that ASPM also localizes to the midbody ring in mammalian cells. ASPM co-localizes with CITK at the midbody ring and coimmunoprecipitates with CITK in lysates prepared from HeLa cells and embryonic neuroepithelium. Furthermore, a GFP-tagged fragment of the N-terminus of ASPM localizes to centrosomes and spindle poles, while a GFP-tagged fragment of the C-terminus localizes to midbodies. All reported ASPM mutations that cause microcephaly involve a truncation or mutation of the C-terminus. In addition, at least two other microcephaly-related proteins, CENPJ and CDK5RAP2, previously localized to spindle poles, also localize to midbodies. Together our observations support a model of neurogenesis in which spindle dynamics and cellular abscission are coordinated.
异常纺锤样小头畸形相关蛋白（ASPM）和西特龙激酶（CITK）的突变分别导致人类和啮齿动物的原发性小头畸形。这两种蛋白均在神经发生过程中表达，并在神经元祖细胞分裂中发挥重要作用。ASPM定位于纺锤体极，对维持增殖性细胞分裂至关重要。CITK存在于胞质分裂沟和中间体环处，对细胞脱离至关重要。我们在此报告，ASPM在哺乳动物细胞中也定位于中间体环。ASPM与CITK在中间体环处共定位，并在从HeLa细胞和胚胎神经上皮制备的裂解物中与CITK共免疫沉淀。此外，ASPM N端的GFP标记片段定位于中心体和纺锤体极，而C端的GFP标记片段定位于中间体。所有导致小头畸形的已报道ASPM突变均涉及C端的截断或突变。此外，至少还有另外两种与小头畸形相关的蛋白，即中心体蛋白J（CENPJ）和细胞周期蛋白依赖性激酶5调节相关蛋白2（CDK5RAP2），先前定位于纺锤体极，现在也定位于中间体。我们的观察结果共同支持了一种神经发生模型，其中纺锤体动力学和细胞脱离是协调的。
