Affiliation:
1. Department of Pharmacology and Center for Neurobiology and Behavior, Columbia University, New York, NY 10032, USA
Abstract
Extracellular cues control the rate and direction of growth of neuronal processes in large part by regulating the cytoskeleton of the growth cone. The actin filament network of the peripheral region is thought to be the primary target for these cues, with consequences for the advance and organization of microtubules. Binding of laminin to integrin receptors is a cue that accelerates the growth of processes from many types of neurons. It was applied acutely to sympathetic neurons in culture to study its effects on the cytoskeleton of the growth cone. Microtubules advance to the edge of the growth cone and bundle in response to laminin, and it was found that small veils of membrane appear near the ends of some of those microtubules. To examine more clearly the relationship between the microtubules and the appearance of actin-rich structures at the periphery, a low dose of cytochalasin D was used to deplete the peripheral region of the growth cone of pre-existing F-actin. The subsequent addition of laminin resulted in the bundling of ends of dynamic (tyrosinated) microtubules at the distal edge of the growth cone, most of which were associated with foci of F-actin. Observations of labeled actin within living growth cones confirmed that these foci formed in response to laminin. Suppression of microtubule dynamics with drugs eliminated the actin foci; washout of drug restored them. Rac 1 did not co-concentrate with F-actin in the peripheral region of the growth cone in the absence of laminin, but did co-concentrate with the foci of F-actin that formed in response to laminin. Inhibition of Rac 1 functioning prevented the formation of the foci and also inhibited laminin-induced neurite growth with or without cytochalasin. These results indicate that extracellular cues can affect actin in the growth cone via microtubules, as well as affect microtubules via actin. They also point to the mediation of microtubule-dependent accumulation of F-actin at the front of the growth cone as a role of Rac 1 in neurite growth.
Publisher
The Company of Biologists
Reference47 articles.
1. Aizawa, H., Wakatsuki, S., Ishii, A., Moriyama, K., Sasaki, Y., Ohashi, K., Sekine-Aizawa, Y., Sehara-Fujisawa, A., Mizuno, K., Goshima, Y. et al. (2001). Phosphorylation of cofilin by LIM-kinase is necessary for semaphorin 3A-induced growth cone collapse. Nat. Neurosci.4,367-373.
2. Bixby, J. L., Lilien, J. and Reichardt, L. F. (1988). Identification of the major proteins that promote neuronal process outgrowth on Schwann cells in vitro. J. Cell Biol.107,353-361.
3. Burden-Gulley, S. M. and Lemmon, V. (1996). L1, N-cadherin, and laminin induce distinct distribution patterns of cytoskeletal elements in growth cones. Cell Motil. Cytoskeleton35,1-23.
4. Challacombe, J. F., Snow, D. M. and Letourneau, P. C. (1996). Actin filament bundles are required for microtubule reorientation during growth cone turning to avoid an inhibitory guidance cue. J. Cell Sci.109,2031-2040.
5. Chamak, B. and Prochiantz, A. (1989). Influence of extracellular matrix proteins on the expression of neuronal polarity. Development106,483-491.
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