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A novel role for doublecortin and doublecortin-like kinase in regulating growth cone microtubules
Journal article   Open access   Peer reviewed

A novel role for doublecortin and doublecortin-like kinase in regulating growth cone microtubules

Daphney C Jean, Peter W Baas and Mark M Black
Human molecular genetics, v 21(26), pp 5511-5527
15 Dec 2012
DOI: https://doi.org/10.1093/hmg/dds395
PMID: 23001563
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1093/hmg/dds395View
Published, Version of Record (VoR) Open

Abstract

Doublecortin (DCX) and doublecortin-like kinase (DCLK), closely related family members, are microtubule-associated proteins with overlapping functions in both neuronal migration and axonal outgrowth. In growing axons, these proteins appear to have their primary functions in the growth cone. Here, we used siRNA to deplete these proteins from cultured rat sympathetic neurons. Normally, microtubules in the growth cone exhibit a gently curved contour as they extend from the base of the cone toward its periphery. However, following depletion of DCX and DCLK, microtubules throughout the growth cone become much more curvy, with many microtubules exhibiting multiple prominent bends over relatively short distances, creating a configuration that we termed wave-like folds. Microtubules with these folds appeared as if they were buckling in response to powerful forces. Indeed, inhibition of myosin-II, which generates forces on the actin cytoskeleton to push microtubules in the growth cone back toward the axonal shaft, significantly decreases the frequency of these wave-like folds. In addition, in the absence of DCX and DCLK, the depth of microtubule invasion into filopodia is reduced compared with controls, and at a functional level, growth cone responses to substrate guidance cues are altered. Conversely, overexpression of DCX results in microtubules that are straighter than usual, suggesting that higher levels of these proteins can enable an even greater resistance to folding. These findings support a role for DCX and DCLK in enabling microtubules to overcome retrograde actin-based forces, thereby facilitating the ability of the growth cone to carry out its crucial path-finding functions.

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42 citations in Web of Science
45 citations in Scopus

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Collaboration types
Domestic collaboration
Web of Science research areas
Biochemistry & Molecular Biology
Genetics & Heredity
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