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

doi:10.1242/jcs.202390

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 language	English
Article number	jcs202390
Pages (from-to)	1-12
Number of pages	12
Journal	Journal of Cell Science
Volume	131
Issue number	1
Early online date	24 Nov 2017
DOIs	https://doi.org/10.1242/jcs.202390
Publication status	Published - 10 Jan 2018

Keywords

PAWS1
FAM83G
CD2AP
Cell migration
Actin cytoskeleton

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10.1242/jcs.202390Licence: CC BY

Final Published VersionFinal published version, 13.3 MBLicence: CC BY

Elucidating the biological function of the uncharacterised protein FAM83G/PAWS1: Role in Wnt signalling through its interaction with Caseine Kinase 1α
Bozatzi, P. (Author), Sapkota, G. (Supervisor), 2018
Student thesis: Doctoral Thesis › Doctor of Philosophy

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Sapkota, Gopal
- MRC PPU - Professor of Disease Signalling
Person: Academic

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Cummins, T. D., Wu, K. Z. L., Bozatzi, P., Dingwell, K. S., Macartney, T. J., Wood, N. T., Varghese, J., Gourlay, R., Campbell, D. G., Prescott, A., Griffis, E., Smith, J. C., & Sapkota, G. P. (2018). PAWS1controls cytoskeletal dynamics and cell migration through association with the SH3 adaptor CD2AP. Journal of Cell Science, 131(1), 1-12. Article jcs202390. https://doi.org/10.1242/jcs.202390

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title = "PAWS1controls cytoskeletal dynamics and cell migration through association with the SH3 adaptor CD2AP",

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.",

keywords = "PAWS1, FAM83G, CD2AP, Cell migration, Actin cytoskeleton",

author = "Cummins, {Timothy D.} and Wu, {Kevin Z. L.} and Polyxeni Bozatzi and Dingwell, {Kevin S.} and Macartney, {Thomas J.} and Wood, {Nicola T.} and Joby Varghese and Robert Gourlay and Campbell, {David G.} and Alan Prescott and Eric Griffis and Smith, {James C.} and Sapkota, {Gopal P.}",

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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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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 - FAM83G

KW - CD2AP

KW - Cell migration

KW - Actin cytoskeleton

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DO - 10.1242/jcs.202390

M3 - Article

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SN - 0021-9533

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JF - Journal of Cell Science

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PAWS1controls cytoskeletal dynamics and cell migration through association with the SH3 adaptor CD2AP

Abstract

Keywords

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Student theses

Elucidating the biological function of the uncharacterised protein FAM83G/PAWS1: Role in Wnt signalling through its interaction with Caseine Kinase 1α

Profiles

Sapkota, Gopal

Cite this