Abl signaling directs growth of a pioneer axon in by shaping the intrinsic fluctuations of actin.

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ID: 85840
2020
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Abstract
The fundamental problem in axon growth and guidance is to understand how cytoplasmic signaling modulates the cytoskeleton to produce directed growth cone motility. In the accompanying paper, we used live imaging of the TSM1 axon of the developing wing to show that the essential role of the core guidance signaling molecule, Abl tyrosine kinase, is to modulate the organization and spatial localization of actin in the advancing growth cone. Here, we dissect in detail the properties of that actin organization, and its consequences for growth cone morphogenesis and motility. We show that advance of the actin mass in the distal axon drives the forward motion of the dynamic filopodial domain that defines the growth cone. We further show that Abl regulates both the width of the actin mass and its internal organization, spatially biasing the intrinsic fluctuations of actin to achieve net advance of the actin, and thus of the dynamic filopodial domain of the growth cone, while maintaining the essential coherence of the actin mass itself. These data suggest a model whereby guidance signaling systematically shapes the intrinsic, stochastic fluctuations of actin in the growth cone to produce axon growth and guidance. [Media: see text] [Media: see text] [Media: see text].
Reference Key
clarke2020ablmolecular Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Clarke, Akanni;McQueen, Philip G;Fang, Hsiao Yu;Kannan, Ramakrishnan;Wang, Victor;McCreedy, Evan;Wincovitch, Stephen;Giniger, Edward;
Journal molecular biology of the cell
Year 2020
DOI
10.1091/mbc.E19-10-0564
URL
Keywords
lung cancer asthma copd pulmonary fibrosis berberine respiratory diseases inflammatory diseases

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