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首页> 外文期刊>Traffic >Activation of the lysosome-associated p61Hck isoform triggers the biogenesis of podosomes
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Activation of the lysosome-associated p61Hck isoform triggers the biogenesis of podosomes

机译：溶酶体相关的p61Hck亚型的激活触发足小体的生物发生。

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Haematopoietic cell kinase (Hck) is a protein tyrosine kinase of the Src family specifically expressed in phagocytes as two isoforms, p59Hck and p61 Hck, present at the plasma membrane and lysosomes, respectively. We report that ectopic expression of a constitutively active mutant of p61Hck (p61Hck(ca)) triggered the de novo formation of actin-rich rings at the ventral face of the cells that we characterized as bona fide podosome rosettes, structures involved in cell migration. Their formation required the adaptor domains and the kinase activity of p61Hck, the integrity of microfilament and microtubule networks and concerted action of Cdc42, Rac and Rho. Podosome rosette formation was either abolished when p61Hck(ca) was readdressed from lysosomes to the cytosol or triggered when p59Hck(ca) was relocalized to lysosomes. Lysosomal markers were present at podosome rosettes. By stimulating exocytosis of p61Hck(ca) lysosomes with a calcium ionophore, the formation of podosome rosettes was enhanced. Interestingly, we confirm that, in human macrophages, Hck and lysosomal markers were present at podosomes which were spatially reorganized as clusters, a foregoing step to form rosettes, upon expression of p61Hck(ca). We propose that lysosomes, under the control of p61Hck, are involved in the biogenesis of podosomes, a key phenomenon in the migration of phagocytes.
机译：造血细胞激酶（Hck）是Src家族的蛋白酪氨酸激酶，在吞噬细胞中特异性表达为两种同工型，即p59Hck和p61 Hck，分别存在于质膜和溶酶体上。我们报告说，p61Hck（p61Hck（ca））的组成型活性突变体的异位表达在我们称为真正足小体玫瑰花结的细胞腹面触发了富含肌动蛋白的环的从头形成，该结构涉及细胞迁移。它们的形成需要衔接子结构域和p61Hck的激酶活性，微丝和微管网络的完整性以及Cdc42，Rac和Rho的协同作用。当p61Hck（ca）从溶酶体重新定位到细胞溶质时，便取消了花体玫瑰花结的形成；或者当p59Hck（ca）重新定位于溶酶体时，触发了花体玫瑰结的形成。溶酶体标记存在于足小体莲座丛上。通过用钙离子载体刺激p61Hck（ca）溶酶体的胞吐作用，可增加足小体玫瑰花结的形成。有趣的是，我们证实，在人类巨噬细胞中，Hck和溶酶体标记存在于空间重组为簇的足小体上，这是表达p61Hck（ca）后形成玫瑰花结的前述步骤。我们建议溶酶体在p61Hck的控制下，参与足小体的生物发生，这是吞噬细胞迁移的关键现象。

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