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
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antigens, CD / chemistry
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Antigens, CD / metabolism
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Calcium / metabolism*
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Calcium-Binding Proteins / chemistry
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Calcium-Binding Proteins / metabolism
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Cell Division
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Cell Line
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Cell Membrane / chemistry
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Cell Membrane / metabolism*
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Cell Membrane / pathology*
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Cells, Cultured
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Collagen / metabolism
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Cricetinae
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Exocytosis*
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Fibroblasts / metabolism
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Fibroblasts / pathology
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Flow Cytometry
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Humans
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Lysosomal Membrane Proteins
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Lysosomes / chemistry
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Lysosomes / metabolism*
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Membrane Glycoproteins / chemistry
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Membrane Glycoproteins / metabolism
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Mice
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Microinjections
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Nerve Tissue Proteins / chemistry
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Nerve Tissue Proteins / metabolism
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Protein Structure, Tertiary
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Rats
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Regeneration / physiology*
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Skin / metabolism
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Skin / pathology
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Synaptotagmins
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Wounds and Injuries / metabolism
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Wounds and Injuries / pathology
Substances
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Antigens, CD
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Calcium-Binding Proteins
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Lysosomal Membrane Proteins
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Membrane Glycoproteins
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Nerve Tissue Proteins
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Synaptotagmins
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Collagen
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Calcium