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

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.
 [1] ;  [1] ;  [1] ;  [1] ;  [1] ;  [1] ;  [2] ;  [3] ;  [4] ;  [1]
  1. St. Jude Children's Research Hospital, Memphis, TN (United States). Department of Developmental Neurobiology
  2. St. Jude Children's Research Hospital, Memphis, TN (United States). Cell & Tissue Imaging Center
  3. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Imaging, Signals and Machine Learning Group
  4. King's College London (United Kingdom). Medical Research Council MRC Centre for Developmental Neurobiology
Publication Date:
Grant/Contract Number:
Accepted Manuscript
Journal Name:
Nature Communications
Additional Journal Information:
Journal Volume: 8; Journal ID: ISSN 2041-1723
Nature Publishing Group
Research Org:
Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
Sponsoring Org:
USDOE; Work for Others (WFO)
Country of Publication:
United States
60 APPLIED LIFE SCIENCES; 59 BASIC BIOLOGICAL SCIENCES; Cell migration; Cytoskeleton; Lamination; Neuronal development
OSTI Identifier: