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