Transmembrane semaphorin5B is proteolytically processed into a repulsive neural guidance cue
Article first published online: 14 AUG 2012
© 2012 The Authors. Journal of Neurochemistry © 2012 International Society for Neurochemistry
Journal of Neurochemistry
Volume 123, Issue 1, pages 135–146, October 2012
How to Cite
Browne, K., Wang, W., Liu, R. Q., Piva, M. and O’Connor, T. P. (2012), Transmembrane semaphorin5B is proteolytically processed into a repulsive neural guidance cue. Journal of Neurochemistry, 123: 135–146. doi: 10.1111/j.1471-4159.2012.07885.x
- Issue published online: 10 SEP 2012
- Article first published online: 14 AUG 2012
- Accepted manuscript online: 21 JUL 2012 12:49AM EST
- Received March 12, 2012; revised manuscript received June 26, 2012; accepted July 9, 2012.
Developing neuronal growth cones respond to a number of post-transcriptionally modified guidance cues to establish functional neural networks. The Semaphorin family has well-established roles as both secreted and transmembrane guidance cues. Here, we describe the first evidence that a transmembrane Semaphorin, Semaphorin 5B (Sema5B), is proteolytically processed from its transmembrane form and can function as a soluble growth cone collapsing guidance cue. Over-expression of A Disintegrin and Metalloprotease (ADAM)-17, results in an enhanced release of the Sema5B ectodomain, while removal of a predicted ADAM-17 cleavage site prevents its release. In contrast, knockdown of ADAM-17 does not significantly reduce Sema5B release, indicating there are additional unknown compensating proteases. This modulation of the transmembrane Sema5B to a diffusible cue represents a sophisticated method to regulate neuronal guidance in vivo.