Plasma membrane repair is mediated by Ca(2+)-regulated exocytosis of lysosomes

Cell. 2001 Jul 27;106(2):157-69. doi: 10.1016/s0092-8674(01)00421-4.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, CD / chemistry
  • Antigens, CD / metabolism
  • Calcium / metabolism*
  • Calcium-Binding Proteins / chemistry
  • Calcium-Binding Proteins / metabolism
  • Cell Division
  • Cell Line
  • Cell Membrane / chemistry
  • Cell Membrane / metabolism*
  • Cell Membrane / pathology*
  • Cells, Cultured
  • Collagen / metabolism
  • Cricetinae
  • Exocytosis*
  • Fibroblasts / metabolism
  • Fibroblasts / pathology
  • Flow Cytometry
  • Humans
  • Lysosome-Associated Membrane Glycoproteins
  • Lysosomes / chemistry
  • Lysosomes / metabolism*
  • Membrane Glycoproteins / chemistry
  • Membrane Glycoproteins / metabolism
  • Mice
  • Microinjections
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / metabolism
  • Protein Structure, Tertiary
  • Rats
  • Regeneration / physiology*
  • Skin / metabolism
  • Skin / pathology
  • Synaptotagmins
  • Wounds and Injuries / metabolism
  • Wounds and Injuries / pathology

Substances

  • Antigens, CD
  • Calcium-Binding Proteins
  • Lysosome-Associated Membrane Glycoproteins
  • Membrane Glycoproteins
  • Nerve Tissue Proteins
  • Synaptotagmins
  • Collagen
  • Calcium