期刊
JOURNAL OF CELL SCIENCE
卷 131, 期 1, 页码 -出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.202390
关键词
PAWS1; FAM83G; CD2AP; Cell migration; Actin cytoskeleton
类别
资金
- UK Medical Research Council Career Development Fellowship
- U.K. MRC Prize PhD studentship
- U.K. Medical Research Council [MC_UU_12016/3]
- AstraZeneca
- Boehringer Ingelheim
- GlaxoSmithKline
- Merck-Serono
- Pfizer
- Janssen
- Francis Crick Institute from Cancer Research UK [FC001157]
- UK Medical Research Council [FC001157]
- Wellcome Trust [FC001157]
- MRC [MC_UU_00018/6, MC_UU_12016/3, MC_U117597140] Funding Source: UKRI
- Medical Research Council [MC_UU_00018/6, MC_UU_12016/3, MC_U117597140] Funding Source: researchfish
- The Francis Crick Institute [10157] Funding Source: researchfish
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 PAWS 1-knockout cells.
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