Tubulin-tyrosine ligase (TTL), the enzyme that catalyzes the addition of a C-terminal tyrosine residue to α-tubulin in the tubulin tyrosination cycle, is involved in tumor progression and has a vital role in neuronal organization. We show that in mammalian fibroblasts, cytoplasmic linker protein (CLIP) 170 and other microtubule plus-end tracking proteins comprising a cytoskeleton-associated protein glycine-rich (CAP-Gly) microtubule binding domain such as CLIP-115 and p150 Glued, localize to the ends of tyrosinated microtubules but not to the ends of detyrosinated microtubules. In vitro, the head domains of CLIP-170 and of p150 Glued bind more efficiently to tyrosinated microtubules than to detyrosinated polymers. In TTL-null fibroblasts, tubulin detyrosination and CAP-Gly protein mislocalization correlate with defects in both spindle positioning during mitosis and cell morphology during interphase. These results indicate that tubulin tyrosination regulates microtubule interactions with CAP-Gly microtubule plus-end tracking proteins and provide explanations for the involvement of TTL in tumor progression and in neuronal organization.
Tubulin tyrosination is a major factor affecting the recruitment of CAP-Gly proteins at microtubule plus ends
Abbreviations used in this paper: CAP-Gly, cytoskeleton-associated protein glycine-rich; CLASP, CLIP-associating protein; CLIP, cytoplasmic linker protein; HD, head domain; MCAK, mitotic centromere-associated kinesin; MEF, mouse embryonic fibroblast; MT, microtubule; TTL, tubulin-tyrosine ligase; TCP, tubulin carboxypeptidase; WT, wild type.
Leticia Peris, Manuel Thery, Julien Fauré, Yasmina Saoudi, Laurence Lafanechère, John K. Chilton, Phillip Gordon-Weeks, Niels Galjart, Michel Bornens, Linda Wordeman, Juergen Wehland, Annie Andrieux, Didier Job; Tubulin tyrosination is a major factor affecting the recruitment of CAP-Gly proteins at microtubule plus ends . J Cell Biol 11 September 2006; 174 (6): 839–849. doi: https://doi.org/10.1083/jcb.200512058
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