臺(tái)灣中央研究院生物醫(yī)學(xué)研究所研究員唐堂教授所在實(shí)驗(yàn)室7月在CPAP蛋白功能研究機(jī)制方面取得新進(jìn)展，相關(guān)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(xué)家們發(fā)現(xiàn) CPAP蛋白（也稱(chēng)CPAP/CENPJ）基因的缺陷會(huì)導(dǎo)致人類(lèi)畸形小頭癥,，研究預(yù)測(cè)可能是神經(jīng)細(xì)胞分裂不正常而影響腦細(xì)胞數(shù)量,，導(dǎo)致患者腦細(xì)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(shí)CPAP具有調(diào)節(jié)細(xì)胞中性粒復(fù)制與成長(zhǎng)的功能，推測(cè)CPAP缺陷可能引發(fā)腦神經(jīng)細(xì)胞中心粒復(fù)制不正常,，導(dǎo)致腦細(xì)胞數(shù)量減少而出現(xiàn)畸形小頭癥,。
唐堂強(qiáng)調(diào)，這項(xiàng)研究雖然是探討非?；A(chǔ)的科學(xué)問(wèn)題,，卻有助于解開(kāi)人類(lèi)、尤其是與腦神經(jīng)細(xì)胞分裂和生長(zhǎng)有關(guān)疾病成因之謎,。
研究團(tuán)隊(duì)在證實(shí)CPAP具有調(diào)控中心粒復(fù)制與成長(zhǎng)功能之后,，目前正積極進(jìn)行CPAP基因剔除小鼠模式實(shí)驗(yàn)，確認(rèn)CPAP蛋白對(duì)中心粒分裂的影響,，是否也會(huì)造成小鼠產(chǎn)生畸形小頭癥,。
研究團(tuán)隊(duì)最重要的貢獻(xiàn)，在于清楚呈現(xiàn)細(xì)胞中心粒分裂過(guò)程,。研究團(tuán)隊(duì)以siRNA降低中心粒的CPAP蛋白表達(dá)量,，就會(huì)抑制細(xì)胞內(nèi)中心粒的復(fù)制與成長(zhǎng)；當(dāng)CPAP濃度過(guò)高時(shí),，反而會(huì)導(dǎo)致基因突變,，引發(fā)細(xì)胞死亡，證實(shí)CPAP具有調(diào)控中心粒復(fù)制與成長(zhǎng)的功能,。
唐堂指出,，學(xué)界已發(fā)現(xiàn)七個(gè)基因突變與畸形小頭癥有關(guān)，其中有三個(gè)位于中心粒上,，研究團(tuán)隊(duì)也因此推論ＣＰＡＰ基因缺陷可能引發(fā)腦神經(jīng)細(xì)胞中心粒復(fù)制不正常,，進(jìn)而影響腦細(xì)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.
