PAWS1 controls cytoskeletal dynamics and cell migration through association with the SH3 adaptor CD2AP.
Timothy D Cummins, Kevin Z L Wu, Polyxeni Bozatzi, Kevin S Dingwell, Thomas J Macartney, Nicola T Wood, Joby Varghese, Robert Gourlay, David G Campbell, Alan Prescott, Eric Griffis, James C Smith, Gopal P Sapkota
Author Information
Timothy D Cummins: Medical Research Council Protein Phosphorylation and Ubiquitylation Unit, Dundee DD1 5EH, UK.
Kevin Z L Wu: Medical Research Council Protein Phosphorylation and Ubiquitylation Unit, Dundee DD1 5EH, UK.
Polyxeni Bozatzi: Medical Research Council Protein Phosphorylation and Ubiquitylation Unit, Dundee DD1 5EH, UK.
Kevin S Dingwell: The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Thomas J Macartney: Medical Research Council Protein Phosphorylation and Ubiquitylation Unit, Dundee DD1 5EH, UK.
Nicola T Wood: Medical Research Council Protein Phosphorylation and Ubiquitylation Unit, Dundee DD1 5EH, UK.
Joby Varghese: Medical Research Council Protein Phosphorylation and Ubiquitylation Unit, Dundee DD1 5EH, UK.
Robert Gourlay: Medical Research Council Protein Phosphorylation and Ubiquitylation Unit, Dundee DD1 5EH, UK.
David G Campbell: Medical Research Council Protein Phosphorylation and Ubiquitylation Unit, Dundee DD1 5EH, UK.
Alan Prescott: Cell Signalling and Immunology, University of Dundee, Dundee DD1 5EH, UK.
Eric Griffis: Centre for Gene Regulation and Expression, University of Dundee, Dundee DD1 5EH, UK. ORCID
James C Smith: The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Gopal P Sapkota: Medical Research Council Protein Phosphorylation and Ubiquitylation Unit, Dundee DD1 5EH, UK g.sapkota@dundee.ac.uk. ORCID
Our previous studies of PAWS1 (protein associated with SMAD1; also known as FAM83G) have suggested that this molecule has roles beyond BMP signalling. To investigate these roles, we have used CRISPR/Cas9 to generate PAWS1-knockout U2OS osteosarcoma cells. Here, we show that PAWS1 plays a role in the regulation of the cytoskeletal machinery, including actin and focal adhesion dynamics, and cell migration. Confocal microscopy and live cell imaging of actin in U2OS cells indicate that PAWS1 is also involved in cytoskeletal dynamics and organization. Loss of PAWS1 causes severe defects in F-actin organization and distribution as well as in lamellipodial organization, resulting in impaired cell migration. PAWS1 interacts in a dynamic fashion with the actin/cytoskeletal regulator CD2AP at lamellae, suggesting that its association with CD2AP controls actin organization and cellular migration. Genetic ablation of CD2AP from U2OS cells instigates actin and cell migration defects reminiscent of those seen in PAWS1-knockout cells.This article has an associated First Person interview with the first authors of the paper.
