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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 and David J. Solecki ()
Additional contact information
Niraj Trivedi: St Jude Children’s Research Hospital
Daniel R. Stabley: St Jude Children’s Research Hospital
Blake Cain: St Jude Children’s Research Hospital
Danielle Howell: St Jude Children’s Research Hospital
Christophe Laumonnerie: St Jude Children’s Research Hospital
Joseph S. Ramahi: St Jude Children’s Research Hospital
Jamshid Temirov: Cell & Tissue Imaging Center, St Jude Children’s Research Hospital
Ryan A. Kerekes: Imaging, Signals and Machine Learning Group, Oak Ridge National Laboratory
Phillip R. Gordon-Weeks: Medical Research Council MRC Centre for Developmental Neurobiology, King's College London
David J. Solecki: St Jude Children’s Research Hospital

Nature Communications, 2017, vol. 8, issue 1, 1-17

Abstract: 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.

Date: 2017
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DOI: 10.1038/ncomms14484

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