title: The distinct roles of the nucleus and nucleus-cytoskeleton connections in three-dimensional cell migration.
abstract: Cells often migrate in vivo in an extracellular matrix that is intrinsically three-dimensional (3D) and the role of actin filament architecture in 3D cell migration is less well understood. Here we show that, while recently identified linkers of nucleoskeleton to cytoskeleton (LINC) complexes play a minimal role in conventional 2D migration, they play a critical role in regulating the organization of a subset of actin filament bundles - the perinuclear actin cap - connected to the nucleus through Nesprin2giant and Nesprin3 in cells in 3D collagen I matrix. Actin cap fibers prolong the nucleus and mediate the formation of pseudopodial protrusions, which drive matrix traction and 3D cell migration. Disruption of LINC complexes disorganizes the actin cap, which impairs 3D cell migration. A simple mechanical model explains why LINC complexes and the perinuclear actin cap are essential in 3D migration by providing mechanical support to the formation of pseudopodial protrusions.
authors: Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, Maryland 21218, USA.
authors: Shyam B
authors: SB
authors: Khatau
authors: Ryan J
authors: RJ
authors: Bloom
authors: Saumendra
authors: S
authors: Bajpai
authors: David
authors: D
authors: Razafsky
authors: Shu
authors: S
authors: Zang
authors: Anjil
authors: A
authors: Giri
authors: Pei-Hsun
authors: PH
authors: Wu
authors: Jorge
authors: J
authors: Marchand
authors: Alfredo
authors: A
authors: Celedon
authors: Christopher M
authors: CM
authors: Hale
authors: Sean X
authors: SX
authors: Sun
authors: Didier
authors: D
authors: Hodzic
authors: Denis
authors: D
authors: Wirtz
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D003599:Cytoskeleton / Q000235:genetics / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D034904:Lamin Type A / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000378:metabolism; D046912:Multiprotein Complexes / Q000378:metabolism; D010641:Phenotype; D034622:RNA Interference
chemical_list: D000199:Actins; D034904:Lamin Type A; D008840:Microfilament Proteins; D046912:Multiprotein Complexes