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Microtubule Redistribution in Growth Cones Elicited by Focal Inactivation of Kinesin-5
Journal article   Open access   Peer reviewed

Microtubule Redistribution in Growth Cones Elicited by Focal Inactivation of Kinesin-5

Vidya C Nadar, Shen Lin and Peter W Baas
The Journal of neuroscience, v 32(17), pp 5783-5794
25 Apr 2012
DOI: https://doi.org/10.1523/JNEUROSCI.0144-12.2012
PMID: 22539840
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1523/JNEUROSCI.0144-12.2012View
Published, Version of Record (VoR) Open

Abstract

In order for growth cones to turn, microtubules from the central domain must preferentially invade the peripheral domain in the direction of the turn. Recent studies suggest that kinesin-5 (also called Eg5 or kif11) suppresses the invasion of microtubules into the peripheral domain on the side of the growth cone opposite the direction of turning. In theory, kinesin-5 could elicit these effects by acting on the microtubules within the peripheral domain itself, by acting on microtubules in the central domain, or in the transition zone between these two domains. In rat neurons expressing kinesin-5, we documented the presence of kinesin-5 in both domains of the growth cone and especially enriched in the transition zone. We then focally inactivated kinesin-5 in various regions of the growth cone, using micro-chromophore-assisted laser inactivation. We found that a greater invasion of microtubules into the peripheral domain occurred when kinesin-5 was inactivated specifically in the transition zone. However, there was no effect on microtubule invasion into the peripheral domain when kinesin-5 was inactivated in the peripheral domain itself or in the central domain. In other experiments, frog growth cones were observed to turn toward a gradient of a drug that inhibits kinesin-5, confirming that asymmetric inactivation of kinesin-5 can cause the growth cone to turn. Finally, expression of a phospho-mutant of kinesin-5 resulted in greater microtubule invasion throughout the peripheral domain and an inhibition of growth cone turning, implicating phosphorylation as a means by which kinesin-5 is regulated in the growth cone.

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