WIP regulates persistence of cell migration and ruffle formation in both mesenchymal and amoeboid modes of motility

• Published in: PloS one 2013-08, Vol.8 (8), p.e70364-e70364
• Main Authors: Banon-Rodriguez, Inmaculada, Saez de Guinoa, Julia, Bernardini, Alejandra, Ragazzini, Chiara, Fernandez, Estefania, Carrasco, Yolanda R, Jones, Gareth E, Wandosell, Francisco, Anton, Ines Maria
• Format: Article
• Language: English
• Subjects: Actin; Adaptor Proteins, Signal Transducing - metabolism; Animals; B cells; B-Lymphocytes - cytology; B-Lymphocytes - drug effects; B-Lymphocytes - metabolism; Biology; Blotting, Western; Carrier Proteins - genetics; Carrier Proteins - metabolism; Cell adhesion & migration; Cell Membrane Structures - metabolism; Cell migration; Cell Movement; Cells, Cultured; Chemokine CXCL13 - pharmacology; Chemokines; Chemotaxis; Chemotaxis - drug effects; CXCL13 protein; Cytoskeletal Proteins; Cytoskeleton; Downstream; Fibroblasts; Fibroblasts - cytology; Fibroblasts - drug effects; Fibroblasts - metabolism; G protein-coupled receptors; Growth factors; Immunology; Kinases; Lamellipodia; Leukocyte migration; Lymphocytes; Lymphocytes B; Mesenchyme; Mice; Mice, 129 Strain; Mice, Knockout; Microscopy, Confocal; Motility; Muscle proteins; Neurosciences; Oncogene Proteins - metabolism; Platelet-derived growth factor; Platelet-Derived Growth Factor - pharmacology; Protein Binding; Proteins; Pseudopodia; Pseudopodia - metabolism; Receptor Protein-Tyrosine Kinases - metabolism; Receptors; Signal transduction; Signaling; Spatial distribution; Stem cells; Tyrosine; Wiskott-Aldrich syndrome; Wiskott-Aldrich Syndrome Protein, Neuronal - metabolism
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0070364

The spatial distribution of signals downstream from receptor tyrosine kinases (RTKs) or G-protein coupled receptors (GPCR) regulates fundamental cellular processes that control cell migration and growth. Both pathways rely significantly on actin cytoskeleton reorganization mediated by nucleation-promoting factors such as the WASP-(Wiskott-Aldrich Syndrome Protein) family. WIP (WASP Interacting Protein) is essential for the formation of a class of polarised actin microdomain, namely dorsal ruffles, downstream of the RTK for PDGF (platelet-derived growth factor) but the underlying mechanism is poorly understood. Using lentivirally-reconstituted WIP-deficient murine fibroblasts we define the requirement for WIP interaction with N-WASP (neural WASP) and Nck for efficient dorsal ruffle formation and of WIP-Nck binding for fibroblast chemotaxis towards PDGF-AA. The formation of both circular dorsal ruffles in PDGF-AA-stimulated primary fibroblasts and lamellipodia in CXCL13-treated B lymphocytes are also compromised by WIP-deficiency. We provide data to show that a WIP-Nck signalling complex interacts with RTK to promote polarised actin remodelling in fibroblasts and provide the first evidence for WIP involvement in the control of migratory persistence in both mesenchymal (fibroblast) and amoeboid (B lymphocytes) motility.