Requirements for exocytosis in permeabilized neuroendocrine cells. Possible involvement of heterotrimeric G proteins associated with secretory vesicles.
Exocytosis in neuroendocrine cells, such as chromaffin cells, is under the regulatory control of heterotrimeric G proteins. LDCV from bovine adrenal medulla contains alpha o-, beta-, and gamma-subunits of G-protein heterotrimers. Probably G proteins associated with the secretory vesicles control the final steps of secretion. G(o), associated with LDCV, could be the pertussis toxin-sensitive G protein that either inhibits exocytosis in PC12 cells or activates it in chromaffin cells. So far, it is unclear whether the other effects of GTP analogues are mediated by heterotrimeric G proteins or by small GTP-binding proteins. The other type of secretory vesicle, SSV from rat brain, also possesses functional sets of G-protein heterotrimers, each consisting of an alpha-, a beta- and a gamma-subunit. In addition to alpha o-subunits, however, alpha i-subunits were found on SSV. Their functional role remains to be determined. Thus, two types of secretory vesicles of the regulated pathway possess functional sets of G-protein heterotrimers. Besides exocytosis, heterotrimeric G proteins on secretory vesicles may control their maturation, transmitter storage, and endocytotic retrieval. So far, it is unclear whether the pattern of G proteins on LDCV and SSV analogues differs within various types of neuroendocrine cells and whether it will change after neoplastic transformation. An altered G-protein setup, not only at the plasma membrane but also on secretory vesicles, may play a role in pathophysiological processes occurring in neuroendocrine cells and tumors derived from them. Such changes might explain the altered secretion observed in neuroendocrine tumor diseases.
Medizinische Klinik und Poliklinik, Abteilung Gastroenterologie, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, Germany.
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Ahnert-Hilger
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Wiedenmann
D000313:Adrenal Medulla / Q000502:physiology; D000818:Animals; D002417:Cattle; D002463:Cell Membrane Permeability; D002837:Chromaffin Granules / Q000502:physiology; D003594:Cytoplasmic Granules / Q000502:physiology*; D005089:Exocytosis; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D046911:Macromolecular Substances; D009490:Neurosecretory Systems / Q000166:cytology / Q000502:physiology*
D046911:Macromolecular Substances; D019204:GTP-Binding Proteins