Doublecortin recognizes the 13-protofilament microtubule cooperatively and tracks microtubule ends.

ABSTRACT: Neurons, like all cells, face the problem that tubulin forms microtubules with too many or too few protofilaments (pfs). Cells overcome this heterogeneity with the γ-tubulin ring complex, which provides a nucleation template for 13-pf microtubules. Doublecortin (DCX), a protein that stabilizes microtubules in developing neurons, also nucleates 13-pf microtubules in vitro. Using fluorescence microscopy assays, we show that the binding of DCX to microtubules is optimized for the lateral curvature of the 13-pf lattice. This sensitivity depends on a cooperative interaction wherein DCX molecules decrease the dissociation rate of their neighbors. Mutations in DCX found in patients with subcortical band heterotopia weaken these cooperative interactions. Using assays with dynamic microtubules, we

SUBMITTER: Bechstedt S 

PROVIDER: S-EPMC3951992 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature