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Journal of Neuroscience, Vol 15, 3400-3407, Copyright © 1995 by Society for Neuroscience
Integrin-cytoskeletal interactions in neuronal growth cones
CE Schmidt, J Dai, DA Lauffenburger, MP Sheetz and AF Horwitz
Department of Chemical Engineering, University of Illinois, Urbana 61801, USA.
Development of the nervous system requires that neuronal growth cones, in
coordination with growing axons, migrate along precise paths defined by
specific extracellular matrix cues until they encounter their targets.
Laminin promotes growth cone migration through receptors such as the
integrins, but the underlying physical mechanism is poorly understood. We
have investigated the cytoskeletal associations and surface dynamics of
endogenous beta 1 integrins in chick dorsal root ganglion growth cones
migrating on laminin. A single-beam optical gradient trap was used to place
0.5-micron-diameter polystyrene beads conjugated with anti-beta 1 integrin
monoclonal antibodies at desired locations on the growth cone surface. We
found a substantial increase in the stable attachment of these beads, with
subsequent slow rearward motion, on the front periphery of the growth cone
compared to the base. The surface dynamics of smaller aggregates of
integrin were explored by monitoring the temporal and spatial displacements
of 40-nm-diameter gold particles coated with anti-beta 1 integrin
antibodies. The small particles were transported preferentially to the
growth cone periphery by brief directed excursions interspersed with
periods of diffusion. In addition, the leading edge of the growth cone was
supported to a greater extent by an actin-dependent cytoskeleton that
resisted mechanical tether formation. Such a regional differentiation of
the growth cone has not been documented previously and has implications for
the mechanism of growth cone migration and guidance.
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