title: Diversified actin protrusions promote environmental exploration but are dispensable for locomotion of leukocytes.
abstract: Most migrating cells extrude their front by the force of actin polymerization. Polymerization requires an initial nucleation step, which is mediated by factors establishing either parallel filaments in the case of filopodia or branched filaments that form the branched lamellipodial network. Branches are considered essential for regular cell motility and are initiated by the Arp2/3 complex, which in turn is activated by nucleation-promoting factors of the WASP and WAVE families. Here we employed rapid amoeboid crawling leukocytes and found that deletion of the WAVE complex eliminated actin branching and thus lamellipodia formation. The cells were left with parallel filaments at the leading edge, which translated, depending on the differentiation status of the cell, into a unipolar pointed cell shape or cells with multiple filopodia. Remarkably, unipolar cells migrated with increased speed and enormous directional persistence, while they were unable to turn towards chemotactic gradients. Cells with multiple filopodia retained chemotactic activity but their migration was progressively impaired with increasing geometrical complexity of the extracellular environment. These findings establish that diversified leading edge protrusions serve as explorative structures while they slow down actual locomotion.
authors: Institute of Science and Technology Austria (IST Austria), am Campus 1, 3400 Klosterneuburg, Austria.
authors: Alexander
authors: A
authors: Leithner
authors: Institute of Science and Technology Austria (IST Austria), am Campus 1, 3400 Klosterneuburg, Austria.
authors: Alexander
authors: A
authors: Eichner
authors: Institute of Science and Technology Austria (IST Austria), am Campus 1, 3400 Klosterneuburg, Austria.|Institute for Molecular Biotechnology, Austrian Academy of Sciences, Dr. Bohr-Gasse 3, 1030 Vienna, Austria.
authors: Jan
authors: J
authors: Müller
authors: Institute of Science and Technology Austria (IST Austria), am Campus 1, 3400 Klosterneuburg, Austria.
authors: Anne
authors: A
authors: Reversat
authors: Institute of Science and Technology Austria (IST Austria), am Campus 1, 3400 Klosterneuburg, Austria.|Clinical Department of Pathology, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
authors: Markus
authors: M
authors: Brown
authors: Institute of Science and Technology Austria (IST Austria), am Campus 1, 3400 Klosterneuburg, Austria.
authors: Jan
authors: J
authors: Schwarz
authors: Institute of Science and Technology Austria (IST Austria), am Campus 1, 3400 Klosterneuburg, Austria.
authors: Jack
authors: J
authors: Merrin
authors: Institute for Molecular Cell Biology, University of Münster, Schlossplatz 5, 48149 Münster, Germany.
authors: David J J
authors: DJ
authors: de Gorter
authors: Institute for Molecular Biotechnology, Austrian Academy of Sciences, Dr. Bohr-Gasse 3, 1030 Vienna, Austria.
authors: Florian
authors: F
authors: Schur
authors: Institute for Molecular Biotechnology, Austrian Academy of Sciences, Dr. Bohr-Gasse 3, 1030 Vienna, Austria.
authors: Jonathan
authors: J
authors: Bayerl
authors: Institute of Science and Technology Austria (IST Austria), am Campus 1, 3400 Klosterneuburg, Austria.
authors: Ingrid
authors: I
authors: de Vries
authors: Institute of Science and Technology Austria (IST Austria), am Campus 1, 3400 Klosterneuburg, Austria.
authors: Stefan
authors: S
authors: Wieser
authors: Institute of Science and Technology Austria (IST Austria), am Campus 1, 3400 Klosterneuburg, Austria.
authors: Robert
authors: http://orcid.org/0000-0001-9843-3522
authors: R
authors: Hauschild
authors: Helmholtz Centre for Infection Research, Inhoffenstrasse 7, 38124 Braunschweig, Germany.
authors: Frank P L
authors: FP
authors: Lai
authors: Department of Molecular Medicine, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.
authors: Markus
authors: M
authors: Moser
authors: Clinical Department of Pathology, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
authors: Dontscho
authors: D
authors: Kerjaschki
authors: Helmholtz Centre for Infection Research, Inhoffenstrasse 7, 38124 Braunschweig, Germany.|Division of Molecular Cell Biology, Zoological Institute, Technische Universität Braunschweig, Spielmannstrasse 7, 38106 Braunschweig, Germany.
authors: Klemens
authors: http://orcid.org/0000-0003-4244-4198
authors: K
authors: Rottner
authors: Institute for Molecular Biotechnology, Austrian Academy of Sciences, Dr. Bohr-Gasse 3, 1030 Vienna, Austria.
authors: J Victor
authors: JV
authors: Small
authors: Institute for Molecular Cell Biology, University of Münster, Schlossplatz 5, 48149 Münster, Germany.|Helmholtz Centre for Infection Research, Inhoffenstrasse 7, 38124 Braunschweig, Germany.
authors: Theresia E B
authors: TE
authors: Stradal
authors: Institute of Science and Technology Austria (IST Austria), am Campus 1, 3400 Klosterneuburg, Austria.
authors: Michael
authors: M
authors: Sixt
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D051376:Actin-Related Protein 2-3 Complex / Q000378:metabolism*; D000199:Actins / Q000378:metabolism; D000818:Animals; D002465:Cell Movement / Q000235:genetics*; D003713:Dendritic Cells / Q000166:cytology*; D007962:Leukocytes / Q000166:cytology*; D051379:Mice; D018345:Mice, Knockout; D058105:Polymerization; D011554:Pseudopodia / Q000378:metabolism
chemical_list: D051376:Actin-Related Protein 2-3 Complex; D000199:Actins