title: Drebrin-mediated microtubule-actomyosin coupling steers cerebellar granule neuron nucleokinesis and migration pathway selection.
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.
authors.affiliation: Department of Developmental Neurobiology, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105, USA.
authors.forename: Niraj
authors.initials: N
authors.lastname: Trivedi
authors.affiliation: Department of Developmental Neurobiology, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105, USA.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Stabley
authors.affiliation: Department of Developmental Neurobiology, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105, USA.
authors.forename: Blake
authors.initials: B
authors.lastname: Cain
authors.affiliation: Department of Developmental Neurobiology, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105, USA.
authors.forename: Danielle
authors.initials: D
authors.lastname: Howell
authors.affiliation: Department of Developmental Neurobiology, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105, USA.
authors.forename: Christophe
authors.initials: C
authors.lastname: Laumonnerie
authors.affiliation: Department of Developmental Neurobiology, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105, USA.
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Ramahi
authors.affiliation: Cell &Tissue Imaging Center, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105, USA.
authors.forename: Jamshid
authors.initials: J
authors.lastname: Temirov
authors.affiliation: Imaging, Signals and Machine Learning Group, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831, USA.
authors.forename: Ryan A
authors.initials: RA
authors.lastname: Kerekes
authors.affiliation: Medical Research Council MRC Centre for Developmental Neurobiology, King's College London, London SE1 1UL, UK.
authors.forename: Phillip R
authors.initials: PR
authors.lastname: Gordon-Weeks
authors.affiliation: Department of Developmental Neurobiology, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Solecki
mesh_terms: D000199:Actins / Q000378:metabolism; D000205:Actomyosin / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement; D002531:Cerebellum / Q000378:metabolism*; D003594:Cytoplasmic Granules / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D008810:Mice, Inbred C57BL; D008853:Microscopy; D008870:Microtubules / Q000378:metabolism*; D053758:Nanoparticles / Q000737:chemistry; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
chemical_list: D000199:Actins; D009479:Neuropeptides; C053386:drebrins; D000205:Actomyosin; C533102:Siah2 protein, mouse; D044767:Ubiquitin-Protein Ligases