Forum 10/16/2003

“A unique mechanism of microtubule stabilization by doublecortin”

Carolyn Moores – BBSRC David Phillips Fellow, School of Crystallography, University of London

Immature neurons undertake an amazing journey from the center of the developing mammalian brain to the outer layers of the cerebral cortex. This migration uses the cell’s general motility machinery, but also a number of molecules which are involved specifically in neuronal path-finding and movement. Doublecortin is one such molecule – it stimulates microtubule polymerization and stabilizes and bundles microtubules, functions which are critical in cell motility. We have used cryo-electron microscopy to visualize the binding site of doublecortin on microtubules which is located between the tubulin protofilaments from which microtubules are built. This unique binding position is ideal for stabilizing the inter-protofilament contacts which hold microtubules together and provides insight into doublecortin’s role in neuronal migration.