Tubulin proteomics: Towards breaking the code

Microtubules (MTs)(2) are dynamic polymers of alpha/beta tubulin heterodimers that are involved in numerous processes such as cell division and migration. MT dynamics is characterized by stochastic transitions between phases of growth and phases of disassembly (catastrophes) and vice versa (pauses and rescues) occurring at the tips of MTs [1]. The resulting basal dynamics is precisely tuned by the expression profile of tubulin isotypes [2], the transient association of proteins to MTs and by the crosstalk between MTs, chromosomes, actin filaments and adhesion sites [3]. MTs also function as a scaffold for a large number of signaling proteins and may serve to localize and regulate their activities. Protein-protein interactions occurring at the surface of MTs have been shown to depend on the extent and nature of tubulin post-translational modifications [4-6]. Progress in deciphering the enzymatic complexes involved in these modifications of tubulin has enabled the development of in vivo models that are key to obtaining insight into the functional significance of this diversity of tubulin species 17,8]. Besides the physiological role of the spatio-temporal expression of different tubulin isotypes, some forms of tubulin have been associated with disease states and therefore represent useful biomarkers [9-13]. These findings underscore the need for advanced qualitative and quantitative analytical approaches allowing the detection of alpha- and beta-tubulin isotype expression ill human cells and tissues. This review will focus on the contributions of high-resolution protein separation and mass spectrometry (VIS) either directly towards this goal or indirectly through the validation of antibodies directed against specific a- or P-tubulin isotypes. The other members of the tubulin family of proteins (gamma, delta, epsilon, and zeta) are not included in this review, but some of the cited principles may be applicable to the analysis of their expression.