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

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

doi:10.1038/ncomms14484

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

Journal Article · Thu Feb 23 00:00:00 EST 2017 · Nature Communications

DOI:https://doi.org/10.1038/ncomms14484· OSTI ID:1346667

Trivedi, Niraj ^[1]; Stabley, Daniel R. ^[1]; Cain, Blake ^[1]; Howell, Danielle ^[1]; Laumonnerie, Christophe ^[1]; Ramahi, Joseph S. ^[1]; Temirov, Jamshid ^[2]; Kerekes, Ryan A. ^[3]; Gordon-Weeks, Phillip R. ^[4]; Solecki, David J. ^[1]

St. Jude Children's Research Hospital, Memphis, TN (United States). Department of Developmental Neurobiology
St. Jude Children's Research Hospital, Memphis, TN (United States). Cell & Tissue Imaging Center
Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Imaging, Signals and Machine Learning Group
King's College London (United Kingdom). Medical Research Council MRC Centre for Developmental Neurobiology

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.

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Research Organization:: Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)

Sponsoring Organization:: USDOE; Work for Others (WFO)

Grant/Contract Number:: AC05-00OR22725

OSTI ID:: 1346667

Journal Information:: Nature Communications, Vol. 8; ISSN 2041-1723

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 33 works

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