C. Hall et al., Collapsin response mediator protein switches RhoA and Rac1 morphology in N1E-115 neuroblastoma cells and is regulated by Rho kinase, J BIOL CHEM, 276(46), 2001, pp. 43482-43486
The formation and directional guidance of neurites involves dynamic regulat
ion of Rho family GTPases. Rac and Cdc42 promote neurite outgrowth, whereas
Rho activation causes neurite retraction. Here we describe a role for coll
apsin response mediator protein (Crmp-2), a neuronal protein implicated in
axonal outgrowth and a component of the semaphorin 3A pathway, in switching
GTPase signaling when expressed in combination with either dominant active
Rac or Rho. In neuroblastoma N1E-115 cells, co-expression of Crmp-2 with d
ominant active RhoA V14 induced Rac morphology, cell spreading and ruffling
(and the formation of neurites). Conversely, co-expression of Crmp-2 with
dominant active Rac1 V12 inhibited Rac morphology, and in cells already exp
ressing Rac1 V12, Crmp-2 caused localized peripheral collapse, involving pi
votal Rho (and Cdc42) activation. Rho kinase was a regulator of Crmp-2; Crm
p-2 phosphorylation was required for Crmp-2/Rac1 V12 inhibition, but not Cr
mp2/RhoA V14 induction, of Rac morphology. Thus Crmp-2, regulated by Rho ki
nase, promotes outgrowth and collapse in response to active Rho and Rac, re
spectively, reversing their usual morphological effects and providing a mec
hanism for dynamic modulation of growth cone guidance.