Direct control of exocytosis by receptor-mediated activation of the heterotrimeric GTPases Gi and G(o) or by the expression of their active G alpha subunits

Details

Serval ID
serval:BIB_E73B545D8B89
Type
Article: article from journal or magazin.
Collection
Publications
Title
Direct control of exocytosis by receptor-mediated activation of the heterotrimeric GTPases Gi and G(o) or by the expression of their active G alpha subunits
Journal
EMBO Journal
Author(s)
Lang  J., Nishimoto  I., Okamoto  T., Regazzi  R., Kiraly  C., Weller  U., Wollheim  C. B.
ISSN
0261-4189 (Print)
Publication state
Published
Issued date
08/1995
Volume
14
Number
15
Pages
3635-44
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Aug 1
Abstract
The exocytotic release of potent hormones is a tightly controlled process. Its direct regulation without the involvement of second messengers would ensure rapid signal processing. In streptolysin O-permeabilized insulin-secreting cells, a preparation allowing dialysis of cytosolic macromolecules, activation of alpha 2-adrenergic receptors caused pertussis toxin-sensitive inhibition of calcium-induced exocytosis. This inhibition was mimicked very efficiently by the use of specific receptor-mimetic peptides, indicating the involvement of Gi and, to a lesser extent, of G(o). The regulation was exerted beyond the ATP-dependent step of exocytosis. In addition, low nanomolar amounts of pre-activated Gi/G(o) directly inhibited exocytosis. As transient overexpression of constitutively active mutants of G alpha i1, G alpha i2, G alpha i3 and G alpha o2 but not of G alpha o1 reproduced this regulation, the G alpha subunit alone is sufficient to induce inhibition. These results define exocytosis as an effector for heterotrimeric G-proteins and delineate the properties of the transduction pathway.
Keywords
Adenosine Triphosphate/physiology Amino Acid Sequence Animals Bacterial Proteins C-Peptide/analysis Calcium/metabolism Cell Line Cell Membrane Permeability Enzyme Activation Epinephrine/pharmacology Exocytosis/drug effects/*physiology GTP Phosphohydrolases/chemistry/*metabolism GTP-Binding Proteins/*metabolism Humans Insulin/secretion Islets of Langerhans/metabolism Molecular Sequence Data Peptides/chemical synthesis/metabolism Pertussis Toxin Rats Receptor, IGF Type 2/metabolism Receptors, Adrenergic, alpha-2/metabolism Signal Transduction/*physiology Streptolysins Virulence Factors, Bordetella/pharmacology
Pubmed
Web of science
Create date
24/01/2008 14:30
Last modification date
20/08/2019 16:10
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