title: From endoplasmic reticulum to secretory granules: role of zinc in the secretory pathway of growth hormone.
abstract: Endocrine and neuroendocrine cells differ from cells which rapidly release all their secreted proteins in that they store some secretory proteins in concentrated forms in secretory granules to be rapidly released when cells are stimulated. Protein aggregation is considered as the first step in the secretory granule biosynthesis and, at least in the case of prolactin and growth hormone, greatly depends on zinc ions that facilitate this process. Hence, regulation of cellular zinc transport especially that within the regulated secretory pathway is of importance to understand. Various zinc transporters of Slc30a/ZnT and Slc39a/Zip families have been reported to fulfil this role and to participate in fine tuning of zinc transport in and out of the endoplasmic reticulum, Golgi complex and secretory granules, the main cellular compartments of the regulated secretory pathway. In this review, we will focus on the role of zinc in the formation of hormone-containing secretory granules with special emphasis on conditions required for growth hormone dimerization/aggregation. In addition, we highlight the role of zinc transporters that govern the process of zinc homeostasis in the regulated hormone secretion.
authors.affiliation: University Children's Hospital, Pediatric Endocrinology, Diabetology and Metabolism, Inselspital, Bern, Switzerland. vibor.petkovic@dkf.unibe.ch
authors.forename: Vibor
authors.initials: V
authors.lastname: Petkovic
authors.forename: Maria Consolata
authors.initials: MC
authors.lastname: Miletta
authors.forename: Primus-E
authors.initials: PE
authors.lastname: Mullis
mesh_terms: D000818:Animals; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D013006:Growth Hormone / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D011485:Protein Binding / Q000187:drug effects; D055503:Protein Multimerization / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D055571:Secretory Pathway / Q000187:drug effects* / Q000502:physiology; D022142:Secretory Vesicles / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D015032:Zinc / Q000494:pharmacology*
chemical_list: D013006:Growth Hormone; D015032:Zinc