PAWS1controls 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 (Lead / Corresponding author)

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Abstract

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.

Original languageEnglish
Article numberjcs202390
Pages (from-to)1-12
Number of pages12
JournalJournal of Cell Science
Volume131
Issue number1
Early online date24 Nov 2017
DOIs
Publication statusPublished - 10 Jan 2018

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Cell Movement
Actins
Clustered Regularly Interspaced Short Palindromic Repeats
Focal Adhesions
Osteosarcoma
Confocal Microscopy
Interviews
Proteins

Keywords

  • PAWS1
  • FAM83G
  • CD2AP
  • Cell migration
  • Actin cytoskeleton

Cite this

Cummins, Timothy D. ; Wu, Kevin Z. L. ; Bozatzi, Polyxeni ; Dingwell, Kevin S. ; Macartney, Thomas J. ; Wood, Nicola T. ; Varghese, Joby ; Gourlay, Robert ; Campbell, David G. ; Prescott, Alan ; Griffis, Eric ; Smith, James C. ; Sapkota, Gopal P. / PAWS1controls cytoskeletal dynamics and cell migration through association with the SH3 adaptor CD2AP. In: Journal of Cell Science. 2018 ; Vol. 131, No. 1. pp. 1-12.
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Cummins, TD, Wu, KZL, Bozatzi, P, Dingwell, KS, Macartney, TJ, Wood, NT, Varghese, J, Gourlay, R, Campbell, DG, Prescott, A, Griffis, E, Smith, JC & Sapkota, GP 2018, 'PAWS1controls cytoskeletal dynamics and cell migration through association with the SH3 adaptor CD2AP', Journal of Cell Science, vol. 131, no. 1, jcs202390, pp. 1-12. https://doi.org/10.1242/jcs.202390

PAWS1controls cytoskeletal dynamics and cell migration through association with the SH3 adaptor CD2AP. / Cummins, Timothy D.; Wu, Kevin Z. L.; Bozatzi, Polyxeni; Dingwell, Kevin S.; Macartney, Thomas J.; Wood, Nicola T.; Varghese, Joby; Gourlay, Robert; Campbell, David G.; Prescott, Alan; Griffis, Eric; Smith, James C.; Sapkota, Gopal P. (Lead / Corresponding author).

In: Journal of Cell Science, Vol. 131, No. 1, jcs202390, 10.01.2018, p. 1-12.

Research output: Contribution to journalArticle

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AU - Cummins, Timothy D.

AU - Wu, Kevin Z. L.

AU - Bozatzi, Polyxeni

AU - Dingwell, Kevin S.

AU - Macartney, Thomas J.

AU - Wood, Nicola T.

AU - Varghese, Joby

AU - Gourlay, Robert

AU - Campbell, David G.

AU - Prescott, Alan

AU - Griffis, Eric

AU - Smith, James C.

AU - Sapkota, Gopal P.

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N2 - 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.

AB - 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.

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KW - CD2AP

KW - Cell migration

KW - Actin cytoskeleton

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DO - 10.1242/jcs.202390

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VL - 131

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JO - Journal of Cell Science

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