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.
Ahnert-Hilger
G
G
Medizinische Klinik und Poliklinik, Abteilung Gastroenterologie, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, Germany.
Wiedenmann
B
B
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