WIP regulates persistence of cell migration and ruffle formation in both mesenchymal and amoeboid modes of motility.
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.
Department of Molecular and Cell Biology, Centro Nacional de Biotecnología, CNB-CSIC, Madrid, Spain.
Inmaculada
I
Banon-Rodriguez
Julia
J
Saez de Guinoa
Alejandra
A
Bernardini
Chiara
C
Ragazzini
Estefania
E
Fernandez
Yolanda R
YR
Carrasco
Gareth E
GE
Jones
Francisco
F
Wandosell
Ines Maria
IM
Anton
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D021961:Cell Membrane Structures / Q000378:metabolism*; D002465:Cell Movement; D002478:Cells, Cultured; D054382:Chemokine CXCL13 / Q000494:pharmacology; D002633:Chemotaxis / Q000187:drug effects; D003598:Cytoskeletal Proteins; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D057507:Mice, 129 Strain; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D015513:Oncogene Proteins / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011485:Protein Binding; D011554:Pseudopodia / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D054382:Chemokine CXCL13; D003598:Cytoskeletal Proteins; C078332:Nck protein; D015513:Oncogene Proteins; D010982:Platelet-Derived Growth Factor; C491671:Waspip protein, mouse; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal; C075278:platelet-derived growth factor A; D020794:Receptor Protein-Tyrosine Kinases