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The Journal of Neuroscience, November 1, 1999, 19(21):9469-9479

The Neural Cell Adhesion Molecules L1 and NCAM-180 Act in Different Steps of Neurite Outgrowth

Kohtaro Takei1, Timothy A. Chan1, Feng-Song Wang1, Haiyan Deng1, Urs Rutishauser2, and Daniel G. Jay1

1 Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, and 2 Program in Biochemistry and Biophysics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021

The formation of neurocircuitry depends on the control of neurite outgrowth that, in turn, can be divided into two processes: nerve growth cone protrusion and neurite extension. It has long been known that the neural cell adhesion molecules L1 and NCAM-180 promote neurite outgrowth, but how they function in growth cones is unclear. We addressed the roles of L1 and NCAM-180 in neurite outgrowth by using microscale chromophore-assisted laser inactivation (micro-CALI) of these proteins to perturb their functions at precise times in single growth cones of embryonic chick dorsal root ganglion neurons grown in culture. Micro-CALI of L1 causes neurite retraction after a 10 min lag period but does not affect growth cone protrusion. In contrast, micro-CALI of NCAM-180 causes rapid growth cone retraction but does not affect neurite extension. The simultaneous inactivation of both these molecules resulted in both distinct effects that were segregated in time. The behavior of growth cones after these micro-CALI treatments resemble the drug-induced perturbation of microtubules for L1 and F-actin for NCAM-180. These findings suggest distinct roles in the growth cone for L1 and NCAM-180 in different steps of neurite outgrowth: L1 functions in neurite extension,whereas NCAM-180 functions in growth cone protrusion.

Key words: CALI (chromophore-assisted laser inactivation); growth cone motility; neurite extension; chick dorsal root ganglion neurons; axon guidance; cell adhesion molecule

Copyright © 1999 Society for Neuroscience  0270-6474/99/19219469-11$05.00/0




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