Control of cell migration by the novel protein phosphatase-2A interacting protein inka2

Hiroki Akiyama, Yumi Iwasaki, Seiya Yamada, Hiroyuki Kamiguchi, Shin ichi Sakakibara

研究成果: Article

抜粋

Cell migration is essential for many physiological and pathological processes, including embryonic development, wound healing, immune response and cancer metastasis. Inka2 transcripts are observed in migrating cells during embryonic development, suggesting the involvement of inka2 in cell migration. However, its precise role remains unclear. Here, we found that inka2 controlled focal adhesion dynamics and cell migration, likely by regulating protein phosphatase-2A (PP2A) function. A scratch assay revealed that inka2 shRNA-transfected NIH3T3 cells showed rapid wound closure, indicating an inhibitory effect by inka2 on cell migration. Live-cell imaging of NIH3T3 cells expressing EGFP-paxillin using total internal reflection fluorescence microscopy revealed that inka2 knockdown increased the turnover rate of focal adhesions. Given that PP2A, which consists of catalytic (C), regulatory (B) and scaffolding (A) subunits, is known to regulate focal adhesions, we examined the inka2-PP2A interaction. Immunoprecipitation revealed an association between inka2 and the PP2A C subunit. Binding of Inka2 to the C subunit prevented the association between the A and C subunits, suggesting that inka2 can inhibit PP2A function. Furthermore, both inka2 expression and PP2A inhibition decreased focal adhesion kinase-paxillin interaction, resulting in reduced formation of focal adhesions. We assessed the effect of pharmacological PP2A inhibition on the inka2 knockdown-induced increase in cell migration speed and found that treatment with a PP2A inhibitor negated the accelerated migration of inka2 knockdown cells. These results suggest that inka2 knockdown exerts its effects through PP2A-dependent regulation of focal adhesions. Our findings contribute to a better understanding of the molecular mechanisms underlying cell migration.

元の言語English
ページ(範囲)527-537
ページ数11
ジャーナルCell and Tissue Research
380
発行部数3
DOI
出版物ステータスPublished - 2020 6 1

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology
  • Cell Biology

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