title: Plasma membrane repair is mediated by Ca(2+)-regulated exocytosis of lysosomes.
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.
authors.affiliation: Section of Microbial Pathogenesis, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: A
authors.initials: A
authors.lastname: Reddy
authors.forename: E V
authors.initials: EV
authors.lastname: Caler
authors.forename: N W
authors.initials: NW
authors.lastname: Andrews
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000737:chemistry / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D002455:Cell Division; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology*; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D006224:Cricetinae; D005089:Exocytosis; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D005434:Flow Cytometry; D006801:Humans; D051907:Lysosomal Membrane Proteins; D008247:Lysosomes / Q000737:chemistry / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D008845:Microinjections; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism; D017434:Protein Structure, Tertiary; D051381:Rats; D012038:Regeneration / Q000502:physiology*; D012867:Skin / Q000378:metabolism / Q000473:pathology; D050857:Synaptotagmins; D014947:Wounds and Injuries / Q000378:metabolism / Q000473:pathology
chemical_list: D015703:Antigens, CD; D002135:Calcium-Binding Proteins; D051907:Lysosomal Membrane Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D050857:Synaptotagmins; D003094:Collagen; D002118:Calcium