The role and mechanism of the GTP-binding protein GE in the control of regulated exocytosis.
Recent advances in the understanding of the terminal stages of the pathway of regulated secretion (exocytosis) have depended in large part on the use of permeabilized secretory cells in which the cytosol is directly accessible to manipulation from the outside. As well as Ca2+, a role for GTP, and hence a GTP-binding protein (GE), is plainly apparent in the exocytotic mechanism of some cells. In metabolically depleted and permeabilized mast cells, the combination of Ca2+ and a guanine nucleotide are a sufficient stimulus for the release of the total cell content of histamine and hexosaminidase. ATP is not required and so a phosphorylation reaction does not comprise a necessary step in the terminal pathway. Phosphorylating nucleotides, however, can modulate the exocytotic reaction in a manner that suggests that the reverse reaction, namely protein dephosphorylation, might be an enabling step. Support for this idea is derived from experiments in which the cells are conditioned to become responsive to Ca2+ alone; in these circumstances the dependence of secretion on the presence of a guanine nucleotide can be reimposed by okadaic acid, an inhibitor of protein phosphatases.
Gomperts
B D
BD
Department of Physiology, University College London, U.K.
Churcher
Y
Y
Koffer
A
A
Kramer
I M
IM
Lillie
T
T
Tatham
P E
PE
D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D003600:Cytosol / Q000378:metabolism; D005089:Exocytosis / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000502:physiology*; D015544:Inositol 1,4,5-Trisphosphate / Q000502:physiology; D008024:Ligands; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism
D008024:Ligands; D015544:Inositol 1,4,5-Trisphosphate; D000255:Adenosine Triphosphate; D011493:Protein Kinase C; D019204:GTP-Binding Proteins