Drebrin-mediated microtubule-actomyosin coupling steers cerebellar granule neuron nucleokinesis and migration pathway selection

Niraj Trivedi, Daniel R Stabley, Blake Cain, Danielle Howell, Christophe Laumonnerie, Joseph S Ramahi, Jamshid Temirov, Ryan A Kerekes, Phillip R Gordon-Weeks, David J Solecki

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38 Citations (Scopus)
154 Downloads (Pure)

Abstract

Neuronal migration from a germinal zone to a final laminar position is essential for the morphogenesis of neuronal circuits. While it is hypothesized that microtubule-actomyosin crosstalk is required for a neuron's 'two-stroke' nucleokinesis cycle, the molecular mechanisms controlling such crosstalk are not defined. By using the drebrin microtubule-actin crosslinking protein as an entry point into the cerebellar granule neuron system in combination with super-resolution microscopy, we investigate how these cytoskeletal systems interface during migration. Lattice light-sheet and structured illumination microscopy reveal a proximal leading process nanoscale architecture wherein f-actin and drebrin intervene between microtubules and the plasma membrane. Functional perturbations of drebrin demonstrate that proximal leading process microtubule-actomyosin coupling steers the direction of centrosome and somal migration, as well as the switch from tangential to radial migration. Finally, the Siah2 E3 ubiquitin ligase antagonizes drebrin function, suggesting a model for control of the microtubule-actomyosin interfaces during neuronal differentiation.

Original languageEnglish
Pages (from-to)14484
JournalNature Communications
Volume8
DOIs
Publication statusPublished - 23 Feb 2017

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