Verdier-Pinard Pascal, Pasquier Eddy, Xiao Hui, Burd Berta, Villard Claude, Lafitte Daniel, Miller Leah M, Angeletti Ruth H, Horwitz Susan Band, Braguer Diane
INSERM UMR 911 CRO2, Aix-Marseille Université, Faculté de Pharmacie, 27 bd Jean Moulin, 13285 Marseille cedex 05, France.
Anal Biochem. 2009 Jan 15;384(2):197-206. doi: 10.1016/j.ab.2008.09.020. Epub 2008 Sep 18.
Since the discovery of tubulin as the major component of microtubules over 40 years ago, its diversity of forms has raised a continuum of fundamental questions about its regulation and functions in a variety of organisms across phyla. Its high abundance in the brain or in specialized organelles such as cilia has allowed early characterization of this important target for anticancer drugs. However, it was only when matrix-assisted laser desorption ionization and electrospray ionization mass spectrometry technologies became available in the late 1980's that the full complexity of tubulin expression patterns became more obvious. This contributed in a major way to the idea that due to increasing and conserved tubulin heterogeneity during evolution, a tubulin code read by microtubule associated proteins might exist and be of functional significance. We review here the merging of recent genetic and cell biology studies with proteomics to decipher this code and illustrate some of the tubulin proteomic approaches with new data generated in our laboratories.
自从40多年前微管蛋白被发现是微管的主要成分以来,其形式的多样性引发了一系列关于其在不同门类生物中的调控和功能的基本问题。它在大脑或诸如纤毛等特殊细胞器中的高丰度,使得抗癌药物的这一重要靶点得以早期表征。然而,直到20世纪80年代末基质辅助激光解吸电离和电喷雾电离质谱技术出现后,微管蛋白表达模式的全部复杂性才变得更加明显。这在很大程度上促成了这样一种观点,即由于进化过程中微管蛋白异质性不断增加且具有保守性,可能存在一种由微管相关蛋白读取的微管蛋白密码,并且具有功能意义。我们在此回顾近期遗传学和细胞生物学研究与蛋白质组学的融合,以解读这一密码,并利用我们实验室产生的新数据阐明一些微管蛋白蛋白质组学方法。