title: Autoinhibition of TBCB regulates EB1-mediated microtubule dynamics.
abstract: Tubulin cofactors (TBCs) participate in the folding, dimerization, and dissociation pathways of the tubulin dimer. Among them, TBCB and TBCE are two CAP-Gly domain-containing proteins that together efficiently interact with and dissociate the tubulin dimer. In the study reported here we showed that TBCB localizes at spindle and midzone microtubules during mitosis. Furthermore, the motif DEI/M-COO(-) present in TBCB, which is similar to the EEY/F-COO(-) element characteristic of EB proteins, CLIP-170, and α-tubulin, is required for TBCE-TBCB heterodimer formation and thus for tubulin dimer dissociation. This motif is responsible for TBCB autoinhibition, and our analysis suggests that TBCB is a monomer in solution. Mutants of TBCB lacking this motif are derepressed and induce microtubule depolymerization through an interaction with EB1 associated with microtubule tips. TBCB is also able to bind to the chaperonin complex CCT containing α-tubulin, suggesting that it could escort tubulin to facilitate its folding and dimerization, recycling or degradation.
authors.affiliation: Departamento de Biología Molecular, Facultad de Medicina, IFIMAV-Universidad de Cantabria, 39011, Santander, Spain.
authors.forename: Gerardo
authors.initials: G
authors.lastname: Carranza
authors.forename: Raquel
authors.initials: R
authors.lastname: Castaño
authors.forename: Mónica L
authors.initials: ML
authors.lastname: Fanarraga
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Villegas
authors.forename: João
authors.initials: J
authors.lastname: Gonçalves
authors.forename: Helena
authors.initials: H
authors.lastname: Soares
authors.forename: Jesus
authors.initials: J
authors.lastname: Avila
authors.forename: Marco
authors.initials: M
authors.lastname: Marenchino
authors.forename: Ramón
authors.initials: R
authors.lastname: Campos-Olivas
authors.forename: Guillermo
authors.initials: G
authors.lastname: Montoya
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Zabala
mesh_terms: D000595:Amino Acid Sequence; D045744:Cell Line, Tumor; D006367:HeLa Cells; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D008938:Mitosis; D018832:Molecular Chaperones / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism; D011485:Protein Binding; D055503:Protein Multimerization; D014404:Tubulin / Q000378:metabolism
chemical_list: C500985:MAPRE1 protein, human; D008869:Microtubule-Associated Proteins; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; C469270:TBCE protein, human; D014404:Tubulin; C501073:tubulin cofactor B, human; C076744:cytoplasmic linker protein 170