Coordination of posttranslational modifications of bovine brain alpha-tubulin. Polyglycylation of delta2 tubulin.
Microtubules participate in a large number of intracellular events including cell division, intracellular transport and secretion, axonal transport, and maintenance of cell morphology. They are composed of tubulin, a heterodimeric protein, consisting of two similar polypeptides alpha and beta. In mammalian cells, both alpha- and beta-tubulin occur as seven to eight different genetic variants, which also undergo numerous posttranslational modifications that include tyrosination-detyrosination and deglutamylation, phosphorylation, acetylation, polyglutamylation, and polyglycylation. Tyrosination-detyrosination is one of the major posttranslational modifications in which the C-terminal tyrosine residue in alpha-tubulin is added or removed reversibly. Although this modification does not alter the assembly activity of tubulin in vitro, these two forms of tubulin have been found to be distributed differently in vivo and are also correlated with microtubule stability (Gunderson, G. G., Kalnoski, M. H., and Bulinski, J. C. (1984) Cell 38, 779-789). Thus, the question arises as to whether these two forms of tubulin differ in any other modifications. In an effort to answer this question, the tyrosinated and the nontyrosinated forms of the alpha1/2 isoform have been purified from brain tubulin by immunoaffinity chromatography. matrix-assisted laser desorption/ionization-time of flight mass spectrometric analysis of the C-terminal peptide revealed that the tyrosinated form is polyglutamylated with one to four Glu residues, while the Delta2 tubulin is polyglycylated with one to three Gly residues. These results indicate that posttranslational modifications of tubulin are correlated with each other and that polyglutamylation and polyglycylation of tubulin may have important roles in regulating microtubule assembly, stability, and function in vivo.
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D008969:Molecular Sequence Data; D010455:Peptides / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism*
D010455:Peptides; D014404:Tubulin; C011080:polyglycine