title: Vimentin organization modulates the formation of lamellipodia.
abstract: Vimentin intermediate filaments (VIF) extend throughout the rear and perinuclear regions of migrating fibroblasts, but only nonfilamentous vimentin particles are present in lamellipodial regions. In contrast, VIF networks extend to the entire cell periphery in serum-starved or nonmotile fibroblasts. Upon serum addition or activation of Rac1, VIF are rapidly phosphorylated at Ser-38, a p21-activated kinase phosphorylation site. This phosphorylation of vimentin is coincident with VIF disassembly at and retraction from the cell surface where lamellipodia form. Furthermore, local induction of photoactivatable Rac1 or the microinjection of a vimentin mimetic peptide (2B2) disassemble VIF at sites where lamellipodia subsequently form. When vimentin organization is disrupted by a dominant-negative mutant or by silencing, there is a loss of polarity, as evidenced by the formation of lamellipodia encircling the entire cell, as well as reduced cell motility. These findings demonstrate an antagonistic relationship between VIF and the formation of lamellipodia.
authors.affiliation: Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
authors.forename: Brian T
authors.initials: BT
authors.lastname: Helfand
authors.forename: Melissa G
authors.initials: MG
authors.lastname: Mendez
authors.forename: S N Prasanna
authors.initials: SN
authors.lastname: Murthy
authors.forename: Dale K
authors.initials: DK
authors.lastname: Shumaker
authors.forename: Boris
authors.initials: B
authors.lastname: Grin
authors.forename: Saleemulla
authors.initials: S
authors.lastname: Mahammad
authors.forename: Ueli
authors.initials: U
authors.lastname: Aebi
authors.forename: Tatjana
authors.initials: T
authors.lastname: Wedig
authors.forename: Yi I
authors.initials: YI
authors.lastname: Wu
authors.forename: Klaus M
authors.initials: KM
authors.lastname: Hahn
authors.forename: Masaki
authors.initials: M
authors.lastname: Inagaki
authors.forename: Harald
authors.initials: H
authors.lastname: Herrmann
authors.forename: Robert D
authors.initials: RD
authors.lastname: Goldman
mesh_terms: D000818:Animals; D002465:Cell Movement; D016764:Cell Polarity; D004926:Escherichia coli; D015870:Gene Expression; D020868:Gene Silencing; D006801:Humans; D007382:Intermediate Filaments / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008845:Microinjections; D041681:NIH 3T3 Cells; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011554:Pseudopodia / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012694:Serine / Q000378:metabolism; D044967:Serum / Q000378:metabolism; D014746:Vimentin / Q000235:genetics / Q000378:metabolism*; D054462:p21-Activated Kinases / Q000235:genetics / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein
chemical_list: D009479:Neuropeptides; D010446:Peptide Fragments; D034741:RNA, Small Interfering; C484602:Rac1 protein, mouse; D011993:Recombinant Fusion Proteins; D014746:Vimentin; D012694:Serine; D054462:p21-Activated Kinases; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein