title: Chromogranin A promotes peptide hormone sorting to mobile granules in constitutively and regulated secreting cells: role of conserved N- and C-terminal peptides.
abstract: Chromogranin A (CgA) has been proposed to play a major role in the formation of dense-core secretory granules (DCGs) in neuroendocrine cells. Here, we took advantage of unique features of the frog CgA (fCgA) to assess the role of this granin and its potential functional determinants in hormone sorting during DCG biogenesis. Expression of fCgA in the constitutively secreting COS-7 cells induced the formation of mobile vesicular structures, which contained cotransfected peptide hormones. The fCgA and the hormones coexpressed in the newly formed vesicles could be released in a regulated manner. The N- and C-terminal regions of fCgA, which exhibit remarkable sequence conservation with their mammalian counterparts were found to be essential for the formation of the mobile DCG-like structures in COS-7 cells. Expression of fCgA in the corticotrope AtT20 cells increased pro-opiomelanocortin levels in DCGs, whereas the expression of N- and C-terminal deletion mutants provoked retention of the hormone in the Golgi area. Furthermore, fCgA, but not its truncated forms, promoted pro-opiomelanocortin sorting to the regulated secretory pathway. These data demonstrate that CgA has the intrinsic capacity to induce the formation of mobile secretory granules and to promote the sorting and release of peptide hormones. The conserved terminal peptides are instrumental for these activities of CgA.
authors.affiliation: Equipe Associée 4310 Neuronal and Neuroendocrine Differentiation and Communication, INSERM U413, European Institute for Peptide Research (IFRMP 23), France.
authors.forename: Maité
authors.initials: M
authors.lastname: Montero-Hadjadje
authors.forename: Salah
authors.initials: S
authors.lastname: Elias
authors.forename: Laurence
authors.initials: L
authors.lastname: Chevalier
authors.forename: Magalie
authors.initials: M
authors.lastname: Benard
authors.forename: Yannick
authors.initials: Y
authors.lastname: Tanguy
authors.forename: Valérie
authors.initials: V
authors.lastname: Turquier
authors.forename: Ludovic
authors.initials: L
authors.lastname: Galas
authors.forename: Laurent
authors.initials: L
authors.lastname: Yon
authors.forename: Maria M
authors.initials: MM
authors.lastname: Malagon
authors.forename: Azeddine
authors.initials: A
authors.lastname: Driouich
authors.forename: Stéphane
authors.initials: S
authors.lastname: Gasman
authors.forename: Youssef
authors.initials: Y
authors.lastname: Anouar
mesh_terms: D029845:Amphibian Proteins / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D001001:Anura; D019556:COS Cells; D002522:Chlorocebus aethiops; D053379:Chromogranin A / Q000096:biosynthesis* / Q000235:genetics; D015870:Gene Expression; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D011333:Pro-Opiomelanocortin / Q000096:biosynthesis / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis* / Q000235:genetics; D022142:Secretory Vesicles / Q000235:genetics / Q000378:metabolism*
chemical_list: D029845:Amphibian Proteins; D053379:Chromogranin A; D010455:Peptides; D011994:Recombinant Proteins; D011333:Pro-Opiomelanocortin