J. Cell Biol., Volume 142, Number 1, July 13, 1998 167-179

STOP Proteins are Responsible for the High Degree of Microtubule Stabilization Observed in Neuronal Cells

Laurent Guillaud, Christophe Bosc, Anne Fourest-Lieuvin, Eric Denarier, Fabienne Pirollet, Laurence Lafanechère, and Didier Job

CEA-Laboratoire du Cytosquelette, INSERM Unité 366, DBMS/CS, CEA-Grenoble, 38054 Grenoble Cedex 9, France

Neuronal differentiation and function require extensive stabilization of the microtubule cytoskeleton. Neurons contain a large proportion of microtubules that resist the cold and depolymerizing drugs and exhibit slow subunit turnover. The origin of this stabilization is unclear. Here we have examined the role of STOP, a calmodulin-regulated protein previously isolated from cold-stable brain microtubules. We find that neuronal cells express increasing levels of STOP and of STOP variants during differentiation. These STOP proteins are associated with a large proportion of microtubules in neuronal cells, and are concentrated on cold-stable, drug-resistant, and long-lived polymers. STOP inhibition abolishes microtubule cold and drug stability in established neurites and impairs neurite formation. Thus, STOP proteins are responsible for microtubule stabilization in neurons, and are apparently required for normal neurite formation.

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