Galanin stimulates neurite outgrowth from sensory neurons by inhibition of Cdc42 and Rho GTPases and activation of cofilin
Article first published online: 22 AUG 2013
© 2013 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of The International Society for Neurochemistry
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Journal of Neurochemistry
Volume 127, Issue 2, pages 199–208, October 2013
How to Cite
J. Neurochem.(2013) 127, 199–208
- Issue published online: 4 OCT 2013
- Article first published online: 22 AUG 2013
- Accepted manuscript online: 29 JUL 2013 09:56AM EST
- Manuscript Accepted: 11 JUL 2013
- Manuscript Revised: 10 JUL 2013
- Manuscript Received: 6 JUN 2013
- Medical Research Council
- The Wellcome Trust
- Diabetes UK
- National Institute on Aging. Grant Number: AG10668
- DRG ;
We and others have previously shown that the neuropeptide galanin modulates neurite outgrowth from adult sensory neurons via activation of the second galanin receptor; however, the intracellular signalling pathways that mediate this neuritogenic effect have yet to be elucidated. Here, we demonstrate that galanin decreases the activation state in adult sensory neurons and PC12 cells of Rho and Cdc42 GTPases, both known regulators of filopodial and growth cone motility. Consistent with this, activated levels of Rho and Cdc42 levels are increased in the dorsal root ganglion of adult galanin knockout animals compared with wildtype controls. Furthermore, galanin markedly increases the activation state of cofilin, a downstream effector of many of the small GTPases, in the cell bodies and growth cones of sensory neurons and in PC12 cells. We also demonstrate a reduction in the activation of cofilin, and alteration in growth cone motility, in cultured galanin knockout neurons compared with wildtype controls. These data provide the first evidence that galanin regulates the Rho family of GTPases and cofilin to stimulate growth cone dynamics and neurite outgrowth in sensory neurons. These findings have important therapeutic implications for the treatment of peripheral sensory neuropathies.
Galanin plays a key role in neurite outgrowth from adult sensory neurons via activation of the second galanin receptor (GalR2). Our results demonstrate the galanin decreases the activation state of Rho and Cdc42 and markedly increases the activation of cofilin. These changes lead to alterations in growth cone motility. These findings have important implications for the treatment of peripheral sensory neuropathies.