title: Actomyosin pulls to advance the nucleus in a migrating tissue cell.
abstract: The cytoskeletal forces involved in translocating the nucleus in a migrating tissue cell remain unresolved. Previous studies have variously implicated actomyosin-generated pushing or pulling forces on the nucleus, as well as pulling by nucleus-bound microtubule motors. We found that the nucleus in an isolated migrating cell can move forward without any trailing-edge detachment. When a new lamellipodium was triggered with photoactivation of Rac1, the nucleus moved toward the new lamellipodium. This forward motion required both nuclear-cytoskeletal linkages and myosin activity. Apical or basal actomyosin bundles were found not to translate with the nucleus. Although microtubules dampen fluctuations in nuclear position, they are not required for forward translocation of the nucleus during cell migration. Trailing-edge detachment and pulling with a microneedle produced motion and deformation of the nucleus suggestive of a mechanical coupling between the nucleus and the trailing edge. Significantly, decoupling the nucleus from the cytoskeleton with KASH overexpression greatly decreased the frequency of trailing-edge detachment. Collectively, these results explain how the nucleus is moved in a crawling fibroblast and raise the possibility that forces could be transmitted from the front to the back of the cell through the nucleus.
authors.affiliation: Department of Chemical Engineering, University of Florida, Gainesville, Florida.
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Chemical Engineering, University of Florida, Gainesville, Florida.
authors.forename: Ian A
authors.initials: IA
authors.lastname: Kent
authors.affiliation: Department of Chemical Engineering, University of Florida, Gainesville, Florida.
authors.forename: Nandini
authors.initials: N
authors.lastname: Shekhar
authors.affiliation: Department of Chemical Engineering, University of Florida, Gainesville, Florida.
authors.forename: T J
authors.initials: TJ
authors.lastname: Chancellor
authors.affiliation: Department of Chemical Engineering, University of Florida, Gainesville, Florida.
authors.forename: Agnes
authors.initials: A
authors.lastname: Mendonca
authors.affiliation: Department of Chemical Engineering, University of Florida, Gainesville, Florida.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Dickinson
authors.affiliation: Department of Chemical Engineering, University of Florida, Gainesville, Florida. Electronic address: tlele@che.ufl.edu.
authors.forename: Tanmay P
authors.initials: TP
authors.lastname: Lele
mesh_terms: D000205:Actomyosin / Q000378:metabolism*; D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism; D002465:Cell Movement; D002467:Cell Nucleus / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D008870:Microtubules / Q000378:metabolism; D009038:Motion; D041681:NIH 3T3 Cells; D011554:Pseudopodia / Q000378:metabolism / Q000502:physiology; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D000205:Actomyosin; D020830:rac1 GTP-Binding Protein