Secretogranin III: a bridge between core hormone aggregates and the secretory granule membrane.
Secretory granules in endocrine cells selectively store bioactive peptide hormones and amines, which are secreted in a regulated manner upon appropriate stimulation. In addition to bioactive substances, various proteins and lipids characteristic of secretory granules are likely recruited to a restricted space at the trans-Golgi Network (TGN), and the space then matures to the secretory granule. Although experimental findings so far have strongly suggested that aggregation- and receptor-mediated processes are essential for the formation of secretory granules, the putative link between these two processes remains to be clarified. Recently, secretogranin III (SgIII) has been identified as a specific binding protein for chromogranin A (CgA), a representative constituent of the core aggregate within secretory granules, and it was later revealed that SgIII can also bind to the cholesterol-rich membrane domain at the TGN. Based on its multifaceted binding properties, SgIII may act as a central player in the formation of cholesterol-rich membrane platforms. Upon these platforms, essential processes for secretory granule biogenesis coordinately occur; that is, selective recruitment of prohormones, processing and modifying of prohormones, and condensation of mature hormones as an aggregate. This review summarizes the findings and theoretical concepts on the issue to date and then focuses on the putative role of SgIII in secretory granule biogenesis in endocrine cells.
Hosaka
Masahiro
M
Department of Molecular Medicine, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan. mhosaka@showa.gunma-u.ac.jp
Watanabe
Tsuyoshi
T
D000818:Animals; D002784:Cholesterol / Q000032:analysis / Q000378:metabolism; D053379:Chromogranin A / Q000378:metabolism; D002864:Chromogranins / Q000502:physiology*; D006728:Hormones / Q000096:biosynthesis / Q000378:metabolism*; D006801:Humans; D007425:Intracellular Membranes / Q000737:chemistry / Q000378:metabolism; D008962:Models, Theoretical; D009479:Neuropeptides / Q000096:biosynthesis; D022142:Secretory Vesicles / Q000502:physiology* / Q000648:ultrastructure*; D021601:trans-Golgi Network / Q000378:metabolism / Q000648:ultrastructure
D053379:Chromogranin A; D002864:Chromogranins; D006728:Hormones; D009479:Neuropeptides; C506167:secretogranin III; D002784:Cholesterol