title: Pro-hormone secretogranin II regulates dense core secretory granule biogenesis in catecholaminergic cells.
abstract: Processes underlying the formation of dense core secretory granules (DCGs) of neuroendocrine cells are poorly understood. Here, we present evidence that DCG biogenesis is dependent on the secretory protein secretogranin (Sg) II, a member of the granin family of pro-hormone cargo of DCGs in neuroendocrine cells. Depletion of SgII expression in PC12 cells leads to a decrease in both the number and size of DCGs and impairs DCG trafficking of other regulated hormones. Expression of SgII fusion proteins in a secretory-deficient PC12 variant rescues a regulated secretory pathway. SgII-containing dense core vesicles share morphological and physical properties with bona fide DCGs, are competent for regulated exocytosis, and maintain an acidic luminal pH through the V-type H(+)-translocating ATPase. The granulogenic activity of SgII requires a pH gradient along this secretory pathway. We conclude that SgII is a critical factor for the regulation of DCG biogenesis in neuroendocrine cells, mediating the formation of functional DCGs via its pH-dependent aggregation at the trans-Golgi network.
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, California 92093-0838. Electronic address: mcourel@univ-rouen.fr.
authors.forename: Maïté
authors.initials: M
authors.lastname: Courel
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, California 92093-0838.
authors.forename: Alex
authors.initials: A
authors.lastname: Soler-Jover
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, California 92093-0838.
authors.forename: Juan L
authors.initials: JL
authors.lastname: Rodriguez-Flores
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, California 92093-0838; Veteran Affairs San Diego Healthcare System, San Diego, California 92093.
authors.forename: Sushil K
authors.initials: SK
authors.lastname: Mahata
authors.affiliation: INSERM U982, University of Rouen, 76821 Mont-St.-Aignan Cedex, France.
authors.forename: Salah
authors.initials: S
authors.lastname: Elias
authors.affiliation: INSERM U982, University of Rouen, 76821 Mont-St.-Aignan Cedex, France.
authors.forename: Maïté
authors.initials: M
authors.lastname: Montero-Hadjadje
authors.affiliation: INSERM U982, University of Rouen, 76821 Mont-St.-Aignan Cedex, France.
authors.forename: Youssef
authors.initials: Y
authors.lastname: Anouar
authors.affiliation: National Center for Microscopy and Imaging Research, University of California San Diego, La Jolla, California 92093.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Giuly
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, California 92093-0838; Veteran Affairs San Diego Healthcare System, San Diego, California 92093. Electronic address: doconnor@ucsd.edu.
authors.forename: Daniel T
authors.initials: DT
authors.lastname: O'Connor
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, California 92093-0838; Veteran Affairs San Diego Healthcare System, San Diego, California 92093. Electronic address: ltaupenot@gmail.com.
authors.forename: Laurent
authors.initials: L
authors.lastname: Taupenot
mesh_terms: D000818:Animals; D019556:COS Cells; D002395:Catecholamines / Q000378:metabolism*; D002522:Chlorocebus aethiops; D002837:Chromaffin Granules / Q000378:metabolism; D020868:Gene Silencing; D005822:Genetic Vectors; D006863:Hydrogen-Ion Concentration; D055099:Neuroendocrine Cells / Q000378:metabolism; D016716:PC12 Cells; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D053381:Secretogranin II / Q000378:metabolism*; D022142:Secretory Vesicles / Q000378:metabolism*
chemical_list: D002395:Catecholamines; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D053381:Secretogranin II