Plasma membrane repair is mediated by Ca2+-regulated exocytosis of lysosomes
Plasma membrane repair is mediated by Ca2+-regulated exocytosis of lysosomes
复制标题
DOI：
10.1016/s0092-8674(01)00421-4
复制
发表时间：
2001-07-27
期刊：
影响因子：
64.5
通讯作者：
Andrews, NW
中科院分区：
文献类型：
--
作者：
Reddy, A;Caler, EV;Andrews, NW
质膜创伤通过涉及Ca 2+调节的胞吐作用的机制修复。细胞内[Ca 2 +]升高触发溶酶体与质膜融合，这是一个由溶酶体突触结合蛋白亚型Syt VII调节的过程。在这里，我们表明，钙离子调节的溶酶体胞吐是必需的质膜破坏的修复。溶酶体胞吐作用和膜再密封被重组Syt VII C（2）A结构域或抗Syt VII C（2）A抗体抑制，或被针对特异性聚集溶酶体的Lamp-1的胞质结构域的抗体抑制。我们进一步证明，溶酶体胞吐介导的原代皮肤成纤维细胞在胶原蛋白基质的收缩过程中受伤的重新密封。这些发现揭示了一个基本的，新的作用溶酶体：作为Ca 2+调节胞吐室负责质膜修复。
Plasma membrane wounds are repaired by a mechanism involving Ca2+-regulated exocytosis. Elevation in intracellular [Ca2+] triggers fusion of lysosomes with the plasma membrane, a process regulated by the lysosomal synaptotagmin isoform Syt VII. Here, we show that Ca2+-regulated exocytosis of lysosomes is required for the repair of plasma membrane disruptions. Lysosomal exocytosis and membrane resealing are inhibited by the recombinant Syt VII C(2)A domain or anti-Syt VII C(2)A antibodies, or by antibodies against the cytosolic domain of Lamp-1, which specifically aggregate lysosomes. We further demonstrate that lysosomal exocytosis mediates the resealing of primary skin fibroblasts wounded during the contraction of collagen matrices. These findings reveal a fundamental, novel role for lysosomes: as Ca2+-regulated exocytic compartments responsible for plasma membrane repair.