Organization of microtubules in axonal growth cones: a role for microtubule-associated protein MAP 1B.

Neuronal growth cones guide growing axons and dendrites (neurites) through developing embryos by detecting extrinsic guidance cues and transducing the signal into changes in motile behaviour. In this brief review, the role of the growth cone cytoskeleton in these events, in particular the microtubules, is discussed. Microtubules in the neurite are mainly bundled into fascicles whereas on entering the growth cone they diverge from each other and traverse the central (C)-domain of the growth cone. Occasionally, individual microtubules extend as far as the peripheral (P)-domain and may even enter filopodia. Microtubules in the growth cone are probably dynamically unstable, exchanging dimer with a large pool of soluble tubulin. It is proposed that the 'capture' of dynamically unstable microtubules by filopodial actin filament bundles is a crucial step underlying directed growth. Localised assembly of microtubules at the growth cone, rather than at the cell body followed by transport of polymer to the growth cone, may facilitate the delivery of material to specific regions of the growth cone and hence allow vectorial growth. Bundling of microtubules and capture of microtubules by filopodia both imply roles for microtubule-associated proteins (MAPs). Several microtubule-associated proteins are present within growth cones, including MAP 1B, MAP2 and tau. Recent experiments point toward a phosphorylated form of MAP 1B as an important component in neurite elongation and in particular in the bundling of microtubules in the growth cone.