台湾中央研究院生物医学研究所研究员唐堂教授所在实验室7月在CPAP蛋白功能研究机制方面取得新进展,相关成果发表在最新一期的Nature cell Biology上。
这是唐堂研究员自2000年首次发现蛋白CPAP后,再次获得CPAP功能研究的成果。2005年,科学家们发现 CPAP蛋白(也称CPAP/CENPJ)基因的缺陷会导致人类畸形小头症,研究预测可能是神经细胞分裂不正常而影响脑细胞数量,导致患者脑细胞数目减少,智力迟缓。
唐堂研究员最新的研究成果正是证实CPAP具有调节细胞中性粒复制与成长的功能,推测CPAP缺陷可能引发脑神经细胞中心粒复制不正常,导致脑细胞数量减少而出现畸形小头症。
唐堂强调,这项研究虽然是探讨非常基础的科学问题,却有助于解开人类、尤其是与脑神经细胞分裂和生长有关疾病成因之谜。
研究团队在证实CPAP具有调控中心粒复制与成长功能之后,目前正积极进行CPAP基因剔除小鼠模式实验,确认CPAP蛋白对中心粒分裂的影响,是否也会造成小鼠产生畸形小头症。
研究团队最重要的贡献,在于清楚呈现细胞中心粒分裂过程。研究团队以siRNA降低中心粒的CPAP蛋白表达量,就会抑制细胞内中心粒的复制与成长;当CPAP浓度过高时,反而会导致基因突变,引发细胞死亡,证实CPAP具有调控中心粒复制与成长的功能。
唐堂指出,学界已发现七个基因突变与畸形小头症有关,其中有三个位于中心粒上,研究团队也因此推论CPAP基因缺陷可能引发脑神经细胞中心粒复制不正常,进而影响脑细胞数量多寡,造成畸形小头症。(生物谷Bioon.com)
生物谷推荐原始出处:
Nature Cell Biology 11, 825 - 831 (2009) 7 June 2009 | doi:10.1038/ncb1889
CPAP is a cell-cycle regulated protein that controls centriole length
Chieh-Ju C. Tang1, Ru-Huei Fu1,3, Kuo-Sheng Wu1,2, Wen-Bin Hsu1 & Tang K. Tang1
Centriole duplication involves the growing of a procentriole (progeny centriole) next to the proximal end of each pre-existing centriole (parental centriole). The molecular mechanisms that regulate procentriole elongation remain obscure. We show here that expression of the centriolar protein CPAP (centrosomal P4.1-associated protein) is carefully regulated during the cell cycle, with the protein being degraded in late mitosis. Depletion of CPAP inhibited centrosome duplication, whereas excess CPAP induced the formation of elongated procentriole-like structures (PLSs), which contain stable microtubules and several centriolar proteins. Ultrastructural analysis revealed that these structures are similar to procentrioles with elongated microtubules. Overexpression of a CPAP mutant (CPAP-377EE) that does not bind to tubulin dimers significantly inhibited the formation of CPAP-induced PLSs. Together, these results suggest that CPAP is a new regulator of centriole length and its intrinsic tubulin-dimer binding activity is required for procentriole elongation.
1 Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.
2 Institute of Biochemistry and Molecular Biology, National Yang Ming University, Taipei 11221, Taiwan.
3 Current address: Graduate Institute of Immunology, China Medical University, Taichung 40402, Taiwan.