Bundling of microtubules in the growth cone induced by laminin

Axons growing in the developing nervous system are guided by cues in the environment which act at the growth cone. So far, the initial cytoskeletal target of these cues has been found to be the network of actin filaments in the peripheral region of the growth cone. Laminins are constituents of the extracellular matrix which promote axonal growth. They exert effects on the actin network. Here, laminin 1 is shown to affect microtubules as well. Acute addition of laminin 1 to rat sympathetic neurons quickly caused the advance of microtubules and their bundling within the initial widely spread growth cone and then the outgrowth of thin, rapidly growing nascent axons. The bundling was pharmacologically separable from the advance of microtubules caused by laminin, as the former but not the latter was blocked by lithium. The bundling did not depend on the peripheral network of actin filaments, as it was unimpaired by the removal of this network with cytochalasin D. Thus, microtubules seem to be a direct cytoskeletal target for laminin 1 in the growth cone, with important consequences for axonal outgrowth.