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

Dev Cell. 2012 Jul 17;23(1):181-92. doi: 10.1016/j.devcel.2012.05.006. Epub 2012 Jun 21.


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 discovered that DCX binds to polymerization intermediates at growing microtubule ends. These results support a mechanism for stabilizing 13-pf microtubules that allows DCX to template new 13-pf microtubules through associations with the sides of the microtubule lattice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Doublecortin Domain Proteins
  • Doublecortin Protein
  • Humans
  • Microtubule-Associated Proteins / chemistry
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism*
  • Microtubules / metabolism*
  • Neurons / metabolism
  • Neuropeptides / chemistry
  • Neuropeptides / genetics
  • Neuropeptides / metabolism*
  • Protein Folding
  • Proteostasis Deficiencies / genetics
  • Proteostasis Deficiencies / metabolism
  • Tubulin / metabolism


  • DCX protein, human
  • Doublecortin Domain Proteins
  • Doublecortin Protein
  • Microtubule-Associated Proteins
  • Neuropeptides
  • Tubulin