title: Accessory subunit Ac45 controls the V-ATPase in the regulated secretory pathway.
abstract: The vacuolar (H(+))-ATPase (V-ATPase) is crucial for multiple processes within the eukaryotic cell, including membrane transport and neurotransmitter secretion. How the V-ATPase is regulated, e.g. by an accessory subunit, remains elusive. Here we explored the role of the neuroendocrine V-ATPase accessory subunit Ac45 via its transgenic expression specifically in the Xenopus intermediate pituitary melanotrope cell model. The Ac45-transgene product did not affect the levels of the prohormone proopiomelanocortin nor of V-ATPase subunits, but rather caused an accumulation of the V-ATPase at the plasma membrane. Furthermore, a higher abundance of secretory granules, protrusions of the plasma membrane and an increased Ca(2+)-dependent secretion efficiency were observed in the Ac45-transgenic cells. We conclude that in neuroendocrine cells Ac45 guides the V-ATPase through the secretory pathway, thereby regulating the V-ATPase-mediated process of Ca(2+)-dependent peptide secretion.
authors.affiliation: Department of Molecular Animal Physiology, Donders Centre for Neuroscience, Faculty of Science, Radboud University, Geert Grooteplein Zuid 28, 6525 GA Nijmegen, The Netherlands.
authors.forename: Eric J R
authors.initials: EJ
authors.lastname: Jansen
authors.forename: Wim J J M
authors.initials: WJ
authors.lastname: Scheenen
authors.forename: Theo G M
authors.initials: TG
authors.lastname: Hafmans
authors.forename: Gerard J M
authors.initials: GJ
authors.lastname: Martens
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000201:enzymology; D025802:Electric Capacitance; D005260:Female; D006056:Golgi Apparatus / Q000201:enzymology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007124:Immunoenzyme Techniques; D047468:Immunoprecipitation; D008297:Male; D010902:Pituitary Gland / Q000166:cytology / Q000201:enzymology*; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D021122:Protein Subunits; D021381:Protein Transport; D055571:Secretory Pathway; D022142:Secretory Vesicles / Q000201:enzymology; D019076:Transgenes / Q000502:physiology; D025262:Vacuolar Proton-Translocating ATPases / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D029867:Xenopus Proteins / Q000502:physiology*; D014982:Xenopus laevis
chemical_list: D021122:Protein Subunits; D029867:Xenopus Proteins; C484227:atp6ap1.1 protein, Xenopus; D049452:Green Fluorescent Proteins; D011333:Pro-Opiomelanocortin; D025262:Vacuolar Proton-Translocating ATPases; D002118:Calcium