Role of cofactors B (TBCB) and E (TBCE) in tubulin heterodimer dissociation.
Tubulin folding cofactors B (TBCB) and E (TBCE) are alpha-tubulin binding proteins that, together with Arl2 and cofactors D (TBCD), A (TBCA or p14) and C (TBCC), participate in tubulin biogenesis. TBCD and TBCE have also been implicated in microtubule dynamics through regulation of tubulin heterodimer dissociation. Understanding the in vivo function of these proteins will shed light on the Kenny-Caffey/Sanjad-Sakati syndrome, an important human disorder associated with TBCE. Here we show that, when overexpressed, TBCB depolymerizes microtubules. We found that this function is based on the ability of TBCB to form a binary complex with TBCE that greatly enhances the efficiency of this cofactor to dissociate tubulin in vivo and in vitro. We also show that TBCE, TBCB and alpha-tubulin form a ternary complex after heterodimer dissociation, whereas the free beta-tubulin subunit is recovered by TBCA. These complexes might serve to escort alpha-tubulin towards degradation or recycling, depending on the cell requirements.
Kortazar
D
D
Unidad de Metabolómica, CICbioGUNE, Parque Tecnológico de Bizkaia, 48160-Derio, Spain.
Fanarraga
M L
ML
Carranza
G
G
Bellido
J
J
Villegas
J C
JC
Avila
J
J
Zabala
J C
JC
D002850:Chromatography, Gel; D019281:Dimerization; D006367:HeLa Cells; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism / Q000502:physiology*; D008870:Microtubules / Q000378:metabolism*; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000378:metabolism / Q000502:physiology*; D046912:Multiprotein Complexes / Q000737:chemistry / Q000302:isolation & purification; D017239:Paclitaxel / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D014162:Transfection; D014404:Tubulin / Q000378:metabolism*; D050257:Tubulin Modulators / Q000494:pharmacology
D008869:Microtubule-Associated Proteins; D018832:Molecular Chaperones; D046912:Multiprotein Complexes; C518713:TBCB protein, mouse; C469270:TBCE protein, human; D014404:Tubulin; D050257:Tubulin Modulators; D017239:Paclitaxel