臺灣中央研究院生物醫(yī)學研究所研究員唐堂教授所在實驗室7月在CPAP蛋白功能研究機制方面取得新進展,，相關成果發(fā)表在最新一期的Nature cell Biology上,。
這是唐堂研究員自2000年首次發(fā)現(xiàn)蛋白CPAP后,，再次獲得CPAP功能研究的成果,。2005年,，科學家們發(fā)現(xiàn) CPAP蛋白（也稱CPAP/CENPJ）基因的缺陷會導致人類畸形小頭癥,，研究預測可能是神經(jīng)細胞分裂不正常而影響腦細胞數(shù)量,，導致患者腦細胞數(shù)目減少,，智力遲緩,。
唐堂研究員最新的研究成果正是證實CPAP具有調節(jié)細胞中性粒復制與成長的功能，推測CPAP缺陷可能引發(fā)腦神經(jīng)細胞中心粒復制不正常,，導致腦細胞數(shù)量減少而出現(xiàn)畸形小頭癥,。
唐堂強調，這項研究雖然是探討非?；A的科學問題,，卻有助于解開人類、尤其是與腦神經(jīng)細胞分裂和生長有關疾病成因之謎,。
研究團隊在證實CPAP具有調控中心粒復制與成長功能之后,，目前正積極進行CPAP基因剔除小鼠模式實驗，確認CPAP蛋白對中心粒分裂的影響,，是否也會造成小鼠產(chǎn)生畸形小頭癥,。
研究團隊最重要的貢獻，在于清楚呈現(xiàn)細胞中心粒分裂過程,。研究團隊以siRNA降低中心粒的CPAP蛋白表達量,，就會抑制細胞內中心粒的復制與成長；當CPAP濃度過高時,，反而會導致基因突變,，引發(fā)細胞死亡,，證實CPAP具有調控中心粒復制與成長的功能。
唐堂指出,，學界已發(fā)現(xiàn)七個基因突變與畸形小頭癥有關,，其中有三個位于中心粒上，研究團隊也因此推論ＣＰＡＰ基因缺陷可能引發(fā)腦神經(jīng)細胞中心粒復制不正常,，進而影響腦細胞數(shù)量多寡,，造成畸形小頭癥。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
