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 language | English |
|---|---|
| Article number | 14484 |
| Journal | Nature Communications |
| Volume | 8 |
| DOIs | |
| State | Published - Feb 23 2017 |
Funding
The Lattice Light Sheet Microscope referenced in this research was used under license from Howard Hughes Medical Institute, Janelia Research Campus. We thank Drs Boyd Butler, Owen Richards, Glen Redford, Karl Kilborn and Colin Monks from 3i for their efforts implementing LLS, James McMurry, Bill Pappas and Andrew Pappas from the St Jude Information Science department for computational support of LLS and Cell and Tissue Imaging Core of St Jude Children's Research Hospital for assistance implementing SR-SIM imaging. Keith A. Laycock, PhD, ELS edited the manuscript. The Solecki Laboratory is funded by the American Lebanese Syrian Associated Charities (ALSAC), by grant #1-FY12-455 from the March of Dimes and by grant 1R01NS066936 from the National Institute Of Neurological Disorders (NINDS). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NINDS or the NIH. The Gordon-Weeks laboratory is supported by the Biotechnology and Biological Sciences Research Council (BBSRC). This manuscript has been authored by UT-Battelle, LLC under Contract No. DE-AC05-00OR22725 with the US Department of Energy.
