title: Cell type-dependent mechanisms for formin-mediated assembly of filopodia.
abstract: Filopodia are finger-like protrusions from the plasma membrane and are of fundamental importance to cellular physiology, but the mechanisms governing their assembly are still in question. One model, called convergent elongation, proposes that filopodia arise from Arp2/3 complex-nucleated dendritic actin networks, with factors such as formins elongating these filaments into filopodia. We test this model using constitutively active constructs of two formins, FMNL3 and mDia2. Surprisingly, filopodial assembly requirements differ between suspension and adherent cells. In suspension cells, Arp2/3 complex is required for filopodial assembly through either formin. In contrast, a subset of filopodia remains after Arp2/3 complex inhibition in adherent cells. In adherent cells only, mDia1 and VASP also contribute to filopodial assembly, and filopodia are disproportionately associated with focal adhesions. We propose an extension of the existing models for filopodial assembly in which any cluster of actin filament barbed ends in proximity to the plasma membrane, either Arp2/3 complex dependent or independent, can initiate filopodial assembly by specific formins.
authors.affiliation: Department of Biochemistry, Geisel School of Medicine at Dartmouth, Hanover, NH 03755.
authors.forename: Lorna E
authors.initials: LE
authors.lastname: Young
authors.affiliation: Department of Biochemistry, Geisel School of Medicine at Dartmouth, Hanover, NH 03755.
authors.forename: Ernest G
authors.initials: EG
authors.lastname: Heimsath
authors.affiliation: Department of Biochemistry, Geisel School of Medicine at Dartmouth, Hanover, NH 03755 henry.higgs@dartmouth.edu.
authors.forename: Henry N
authors.initials: HN
authors.lastname: Higgs
mesh_terms: D008841:Actin Cytoskeleton / Q000235:genetics / Q000378:metabolism; D051376:Actin-Related Protein 2-3 Complex / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism; D003712:Dendrites / Q000235:genetics / Q000378:metabolism; D000080865:Formins; D006801:Humans; D019169:Jurkat Cells; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D011554:Pseudopodia / Q000235:genetics* / Q000378:metabolism; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: D051376:Actin-Related Protein 2-3 Complex; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; C491462:DIAPH2 protein, human; C476209:FMNL3 protein, human; D000080865:Formins; D008840:Microfilament Proteins; D010750:Phosphoproteins; D011506:Proteins; D000098662:Vasodilator-Stimulated Phosphoprotein