Adhesion-dependent Caveolin-1 Tyrosine-14 phosphorylation is regulated by FAK in response to changing matrix stiffness.

IF 3 4区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

FEBS Letters Pub Date : 2021-02-01 Epub Date: 2021-01-17 DOI:10.1002/1873-3468.14025

Natasha Buwa, Nivedhika Kannan, Shaunak Kanade, Nagaraj Balasubramanian

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引用次数: 2

Abstract

Integrin-mediated adhesion regulates cellular responses to changes in the mechanical and biochemical properties of the extracellular matrix. Cell-matrix adhesion regulates caveolar endocytosis, dependent on caveolin 1 (Cav1) Tyr14 phosphorylation (pY14Cav1), to control anchorage-dependent signaling. We find that cell-matrix adhesion regulates pY14Cav1 levels in mouse fibroblasts. Biochemical fractionation reveals endogenous pY14Cav1 to be present in caveolae and focal adhesions (FA). Adhesion does not affect caveolar pY14Cav1, supporting its regulation at FA, in which PF-228-mediated inhibition of focal adhesion kinase (FAK) disrupts. Cell adhesion on 2D polyacrylamide matrices of increasing stiffness stimulates Cav1 phosphorylation, which is comparable to the phosphorylation of FAK. Inhibition of FAK across varying stiffnesses shows it regulates pY14Cav1 more prominently at higher stiffness. Taken together, these studies reveal the presence of FAK-pY14Cav1 crosstalk at FA, which is regulated by cell-matrix adhesion.

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粘附依赖性Caveolin-1酪氨酸-14磷酸化受FAK调节，以响应基质刚度的变化。

整合素介导的粘附调节细胞对细胞外基质机械和生化特性变化的反应。细胞-基质粘附调节腔泡内吞作用，依赖于腔泡蛋白1 (Cav1) Tyr14磷酸化(pY14Cav1)，以控制锚定依赖性信号。我们发现细胞-基质粘附调节小鼠成纤维细胞中pY14Cav1的水平。生化分离显示内源性pY14Cav1存在于小泡和局灶粘连(FA)中。粘附不影响空泡pY14Cav1，支持其在FA的调控，其中pf -228介导的局灶粘附激酶(FAK)抑制被破坏。细胞粘附在刚度增加的二维聚丙烯酰胺基质上刺激Cav1磷酸化，这与FAK的磷酸化相当。FAK在不同刚度下对pY14Cav1的抑制作用表明，FAK在高刚度下对pY14Cav1的调节作用更为显著。综上所述，这些研究揭示了FA中存在FAK-pY14Cav1串扰，该串扰受细胞-基质粘附调节。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

FEBS Letters 生物-生化与分子生物学

CiteScore

6.60

自引率

2.90%

发文量

303

审稿时长

1 months

期刊介绍： FEBS Letters is one of the world''s leading journals in molecular biology and is renowned both for its quality of content and speed of production. Bringing together the most important developments in the molecular biosciences, FEBS Letters provides an international forum for Minireviews, Research Letters and Hypotheses that merit urgent publication.