Mori R, Toda T

Supplying a proper amount of correctly folded α/β-tubulin heterodimers is critical for microtubule dynamics. Formation of assembly-competent heterodimers is remarkably elaborate at the molecular level, in which the α- and β-tubulins are separately processed in a chaperone-dependent manner. This sequential step is performed by the tubulin folding cofactor pathway, comprising ...

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of a specific set of regulatory proteins - cofactors A to E. We have identified the fission yeast cofactor - the ortholog of cofactor C, Tbc1. As well as its roles in tubulin folding, Tbc1 also has another role as a GAP in regulating Alp41/Arl2, a highly conserved small GTPase. Interestingly, the expression of either GDP- or GTP- bound Alp41 showed the identical microtubule loss phenotype, suggesting that the continuous cycling between these forms is important for its functions. In addition, we have identified that Alp41 interacts with Alp1(D) - the ortholog of cofactor D, specifically when in the GDP bound form. Intriguingly, Alp1(D) colocalizes with microtubules when in excess, eventually leading to depolymerization, which is sequestered by cooverproducing GDP-bound Alp41. We present a model of the final stages of the tubulin cofactor pathway, where we observe a dual role for both Tbc1 and Alp1(D) in opposing regulations of the microtubule.

Date: Apr. 10, 2013

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