ALS2/Alsin regulates Rac-PAK signaling and neurite outgrowth.
Citation:
Tudor, EL, Perkinton, MS, Schmidt, A, Ackerley, S, Brownlees, J, Jacobsen, NJ, Byers, HL, Ward, M, Hall, A, Leigh, PN, Shaw, CE, McLoughlin, DM, Miller, CC, `ALS2/Alsin regulates Rac-PAK signaling and neurite outgrowth? in The Journal of Biological Chemistry, 280, (41), 2005, pp 34735 - 34740Download Item:
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Abstract:
Rac and its downstream effectors p21-activated kinase (PAK)
family kinases regulate actin dynamics within growth cones to control
neurite outgrowth during development. The activity of Rac is
stimulated by guanine nucleotide exchange factors (GEFs) that promote
GDP release and GTP binding. ALS2/Alsin is a recently
described GEF that contains a central domain that is predicted to
regulate the activities of Rac and/or Rho and Cdc42 activities. Mutations
in ALS2 cause some recessive familial forms of amyotrophic
lateral sclerosis (ALS) but the function of ALS2 is poorly understood.
Here we demonstrate that ALS2 is present within growth
cones of neurons, in which it co-localizes with Rac. Furthermore,
ALS2 stimulates Rac but not Rho or Cdc42 activities, and this
induces a corresponding increase in PAK1 activity. Finally, we demonstrate
that ALS2 promotes neurite outgrowth. Defects in these
functions may therefore contribute to motor neuron demise in ALS.
Sponsor
Grant Number
Medical Research Council
Author's Homepage:
http://people.tcd.ie/mclougdeDescription:
PUBLISHED
Author: MCLOUGHLIN, DECLAN
Publisher:
American Society for Biochemistry and Molecular BiologyType of material:
Journal ArticleCollections:
Series/Report no:
The Journal of Biological Chemistry280
41
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