Reddy A, Caler E V, Andrews N W
Section of Microbial Pathogenesis, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
Cell. 2001 Jul 27;106(2):157-69. doi: 10.1016/s0092-8674(01)00421-4.
Plasma membrane wounds are repaired by a mechanism involving Ca(2+)-regulated exocytosis. Elevation in intracellular [Ca(2+)] triggers fusion of lysosomes with the plasma membrane, a process regulated by the lysosomal synaptotagmin isoform Syt VII. Here, we show that Ca(2+)-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 Ca(2+)-regulated exocytic compartments responsible for plasma membrane repair.
质膜伤口通过一种涉及Ca(2+)调节的胞吐作用的机制进行修复。细胞内[Ca(2+)]的升高触发溶酶体与质膜的融合，这一过程由溶酶体突触结合蛋白异构体Syt VII调节。在这里，我们表明溶酶体的Ca(2+)调节的胞吐作用是质膜破坏修复所必需的。重组Syt VII C(2)A结构域或抗Syt VII C(2)A抗体，或针对Lamp-1胞质结构域的抗体（其特异性聚集溶酶体）可抑制溶酶体胞吐作用和膜重新封闭。我们进一步证明，溶酶体胞吐作用介导了在胶原基质收缩过程中受伤的原代皮肤成纤维细胞的重新封闭。这些发现揭示了溶酶体的一个基本的新作用：作为负责质膜修复的Ca(2+)调节的胞吐区室。
