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WORKSHOP ON:
CENTRAL PROBLEMS IN SINGLE CELL COMPUTATION
16-18 September 2002
By invitation only
Venue
B10 Seminar Room, Alexandra House, 17 Queen Square, London, WC1N 3AR
| Control of growth cone steering by
local protein synthesis and degradation |
| Christine Holt, Anatomy
Department, University of Cambridge, UK |
| Growth cones navigate using a variety of
molecular cues that punctuate the early axonal pathways in the brain. The retinal growth
cones of Xenopus exhibit fast chemotropic responses to guidance factors such as
netrin-1 and Sema3A in vitro enabling the mechanisms underlying steering to be explored.
Growth cones isolated from their cell bodies are able to navigate correctly along the
visual pathway in vivo and to respond chemotropically to guidance factors in vitro
indicating that the steering mechanisms are driven locally and do not require the soma.
Growth cones contain an abundance of mRNAs, translation machinery and also protein
degradation machinery. We show that retinal growth cones isolated from their cell bodies
lose their ability to turn in a chemotropic gradient of netrin-1 or Sema3A when
translation is blocked. Translation inhibition also prevents Sema3A-induced collapse while
LPA-induced collapse is not affected. Inhibition of proteasome function blocks responses
to netrin-1 and LPA but does not affect Sema3A responses. We further demonstrate that
netrin-1 and Sema3A activate translation initiation factors and stimulate a marked rise in
protein synthesis within minutes while netrin-1 and LPA elicit similar rises in
ubiquitin-protein conjugates. Our results suggest that guidance molecules steer axon
growth by triggering rapid and local changes in protein levels in growth cones. |
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