Tubulin tyrosination is a major factor affecting the recruitment of CAP-Gly proteins at microtubule plus ends.
Tubulin-tyrosine ligase (TTL), the enzyme that catalyzes the addition of a C-terminal tyrosine residue to alpha-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.
Peris
Leticia
L
Laboratoire du Cytosquelette, Institut National de la Santé et de la Recherche Médicale U366, Département Réponse et Dynamique Cellulaire, Commisariat à l'Energie Atomique Grenoble, 38054 Grenoble, France.
Thery
Manuel
M
Fauré
Julien
J
Saoudi
Yasmina
Y
Lafanechère
Laurence
L
Chilton
John K
JK
Gordon-Weeks
Phillip
P
Galjart
Niels
N
Bornens
Michel
M
Wordeman
Linda
L
Wehland
Juergen
J
Andrieux
Annie
A
Job
Didier
D
D000818:Animals; D002478:Cells, Cultured; D000072159:Dynactin Complex; D005347:Fibroblasts / Q000378:metabolism* / Q000648:ultrastructure; D007399:Interphase / Q000502:physiology; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism* / Q000648:ultrastructure; D009363:Neoplasm Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010453:Peptide Synthases / Q000235:genetics / Q000378:metabolism; D011108:Polymers / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000502:physiology; D008941:Spindle Apparatus / Q000378:metabolism / Q000648:ultrastructure; D014404:Tubulin / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*
C000606364:Dctn1 protein, mouse; D000072159:Dynactin Complex; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D011108:Polymers; D014404:Tubulin; C109878:cytoplasmic linker protein 115; C076744:cytoplasmic linker protein 170; D014443:Tyrosine; D010453:Peptide Synthases; C112698:tubulin polyglutamylase