title: Brief exposure to copper activates lysosomal exocytosis.
abstract: Copper (Cu) is essential mineral, but its toxicity necessitates existence of powerful machinery responsible for the extraction of excess Cu from the cell. Cu exposure was recently shown to induce the translocation of Cu pump ATP7B to the lysosomes followed by lysosomal exocytosis. Here we sought to investigate the mechanisms underlying the effect of Cu on lysosomal exocytosis. We found that brief exposure to Cu activates lysosomal exocytosis, which was measured as a release of the lysosomal digestive enzyme β-hexosaminidase (β-hex) into the extracellular medium and by the presence lysosomal protein LAMP1 at the plasma membrane. Such release depends on calcium (Ca) and on the lysosomal SNARE VAMP7. ATP7B knockdown using RNAi suppressed the basal lysosomal exocytosis, but did not affect the ability of Cu to activate it. ATP7B knockdown was associated with sustained oxidative stress. The removal of Ca from the extracellular medium suppressed the Cu-dependent component of the lysosomal exocytosis. We propose that Cu promotes lysosomal exocytosis by facilitating a Ca-dependent step of the lysosomal exocytosis.
authors.affiliation: Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, United States.
authors.forename: Karina
authors.initials: K
authors.lastname: Peña
authors.affiliation: Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, United States.
authors.forename: Jessica
authors.initials: J
authors.lastname: Coblenz
authors.affiliation: Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, United States. Electronic address: Kiselyov@pitt.edu.
authors.forename: Kirill
authors.initials: K
authors.lastname: Kiselyov
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D003300:Copper / Q000494:pharmacology*; D000073840:Copper-Transporting ATPases; D005089:Exocytosis / Q000187:drug effects / Q000235:genetics; D005110:Extracellular Space / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D052118:Lysosomal-Associated Membrane Protein 1 / Q000378:metabolism; D008247:Lysosomes / Q000187:drug effects* / Q000502:physiology; D018384:Oxidative Stress / Q000235:genetics; D021381:Protein Transport; D050683:R-SNARE Proteins / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism
chemical_list: D027682:Cation Transport Proteins; D052118:Lysosomal-Associated Membrane Protein 1; D050683:R-SNARE Proteins; D034741:RNA, Small Interfering; C121241:VAMP7 protein, human; D003300:Copper; D001619:beta-N-Acetylhexosaminidases; D000251:Adenosine Triphosphatases; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases; D002118:Calcium
keywords: Calcium; Copper; Exocytosis; Lysosomes