title: Cytoplasmic dynein pushes the cytoskeletal meshwork forward during axonal elongation.
abstract: During development, neurons send out axonal processes that can reach lengths hundreds of times longer than the diameter of their cell bodies. Recent studies indicate that en masse microtubule translocation is a significant mechanism underlying axonal elongation, but how cellular forces drive this process is unknown. Cytoplasmic dynein generates forces on microtubules in axons to power their movement through 'stop-and-go' transport, but whether these forces influence the bulk translocation of long microtubules embedded in the cytoskeletal meshwork has not been tested. Here, we use both function-blocking antibodies targeted to the dynein intermediate chain and the pharmacological dynein inhibitor ciliobrevin D to ask whether dynein forces contribute to en bloc cytoskeleton translocation. By tracking docked mitochondria as fiducial markers for bulk cytoskeleton movements, we find that translocation is reduced after dynein disruption. We then directly measure net force generation after dynein disruption and find a dramatic increase in axonal tension. Taken together, these data indicate that dynein generates forces that push the cytoskeletal meshwork forward en masse during axonal elongation.
authors.affiliation: Cell and Molecular Biology Program, Michigan State University, 288 Farm Ln Room 336, East Lansing, MI 48824, USA.
authors.forename: Douglas H
authors.initials: DH
authors.lastname: Roossien
authors.affiliation: Department of Zoology, Michigan State University, 288 Farm Ln Room 336, East Lansing, MI 48824, USA.
authors.forename: Phillip
authors.initials: P
authors.lastname: Lamoureux
authors.affiliation: Department of Zoology, Michigan State University, 288 Farm Ln Room 336, East Lansing, MI 48824, USA kmiller@msu.edu.
authors.forename: Kyle E
authors.initials: KE
authors.lastname: Miller
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D002645:Chickens; D056445:Cytoplasmic Dyneins / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D021381:Protein Transport
chemical_list: D056445:Cytoplasmic Dyneins
keywords: Axonal elongation; Dynein; Neuronal biophysics