首页> 外文期刊>Journal of dermatological science >Actin dynamics regulate immediate PAR-2-dependent responses to acute epidermal permeability barrier abrogation.
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Actin dynamics regulate immediate PAR-2-dependent responses to acute epidermal permeability barrier abrogation.

机译:肌动蛋白动力学调节对急性表皮通透性屏障废除的即时PAR-2依赖性反应。

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BACKGROUND: Lamellar body (LB) secretion and terminal differentiation of stratum granulosum (SG) cells are signaled by both protease activated receptor-2 (PAR-2) and caveolin-1 (cav-1). OBJECTIVE: To address the early dynamics of LB secretion, we examined cytoskeletal remodeling of keratinocytes in 3 mouse models following acute barrier abrogation: hairless mice, PAR-2 knockout (-/-) and cav-1 -/-. METHODS AND RESULTS: Under basal conditions, globular (G)-actin accumulates in SG cells cytosol, while filamentous (F)-actin is restricted to peri-membrane domains. Barrier abrogation induces the apical movement of F-actin and the retreat of the SG-G-actin front, paralleled by upstream cytoskeletal kinases activation. This phenomenon was both enhanced by PAR-2 agonist, and inhibited by cytochalasin-D and in PAR-2 knockout mice. We found that plasma membrane conformational changes causing LB secretion are controlled by PAR-2-dependent cytoskeletal rearrangements. We next addressed the interaction dynamics between cytoskeleton and plasma membrane following PAR-2-induced actin stress fiber formation in both cav-1 -/- and wildtype cells. Actin stress fiber formation is increased in cav-1 -/- cells prior to and following PAR-2 agonist peptide-treatment, while absence of cav-1 inhibits E-cadherin-mediated cell-to-cell adhesion. CONCLUSION: PAR-2 drives cytoskeletal/plasma membrane dynamics that regulate early LB secretion following barrier abrogation, stress fiber formation and keratinocyte adhesion.
机译:背景:层状体(LB)分泌和颗粒层(SG)细胞的终末分化是由蛋白酶激活受体2(PAR-2)和小窝蛋白1(cav-1)发出的。目的:为了解决LB分泌的早期动态,我们检查了急性障碍消除后3种小鼠模型中角质形成细胞的细胞骨架重塑:无毛小鼠,PAR-2敲除(-/-)和cav-1-/-。方法和结果:在基础条件下,球状(G)-肌动蛋白在SG细胞的细胞质中积聚,而丝状(F)-肌动蛋白则局限于膜周结构域。屏障的消除引起F-肌动蛋白的顶端运动和SG-G-肌动蛋白前沿的后退,同时上游细胞骨架激酶激活。在PAR-2敲除小鼠中,这种现象既被PAR-2激动剂增强,又被细胞松弛素D抑制。我们发现,引起LB分泌的质膜构象变化受PAR-2依赖性细胞骨架重排控制。接下来,我们研究了在cav-1-/-和野生型细胞中PAR-2-诱导的肌动蛋白应激纤维形成后细胞骨架与质膜之间的相互作用动力学。在PAR-2激动剂肽处理之前和之后,cav-1-/-细胞中肌动蛋白应激纤维的形成增加,而cav-1的缺乏则抑制E-钙粘蛋白介导的细胞间粘附。结论:PAR-2驱动细胞骨架/质膜动力学,调节屏障消除,应激纤维形成和角质形成细胞粘附后的早期LB分泌。

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