Drebrin-mediated microtubule–actomyosin coupling steers cerebellar granule neuron nucleokinesis and migration pathway selection
Year: 2017
Type: article
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.
Source: Nature Communications
DOI: 10.1038/ncomms14484
Language: English
Subfield: Developmental Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Funders: U.S. Department of Energy, March of Dimes Foundation, Battelle, American Lebanese Syrian Associated Charities, UT-Battelle, National Institutes of Health, Directorate for Biological Sciences, Biotechnology and Biological Sciences Research Council, National Institute of Neurological Disorders and Stroke
Awards: G1026679911, G1645119126, G166562317, G1696177674, G203625172, G2584197162, G2757267231, Polarity Signals Coordinate Neuronal Migration and Germinal Zone Exit, G2909414793, G2988778103, G3049477530, G313676650, G411266785, Breaking Cellular Symmetry: Intracellular Pathways Underlying Neuritogenesis, G5726405315, G6911681599, G7769062580, G8385026264, G8830688781, G8906985441, G8943143067
OpenAlex ID: W2588362877