In:
The Journal of Neuroscience, Society for Neuroscience, Vol. 27, No. 1 ( 2007-01-03), p. 190-202
Kurzfassung:
Although it has been established that the activation of GTPases by non-hydrolyzable GTP stimulates neurotransmitter release from many different secretory cell types, the underlying mechanisms remain unclear. In the present study we aimed to elucidate the functional role(s) for endogenous Ras-like protein A (RalA) and RalB GTPases in GTP-dependent exocytosis. For this purpose stable neuroendocrine pheochromocytoma 12 (PC12) cell lines were generated in which the expressions of both RalA and RalB were strongly downregulated. In these double knock-down cells GTP-dependent exocytosis was reduced severely and was restored after the expression of RalA or RalB was reintroduced by transfection. In contrast, Ca 2+ -dependent exocytosis and the docking of dense core vesicles analyzed by electron microscopy remained unchanged in the double knock-down cells. Furthermore, the transfected RalA and RalB appeared to be localized primarily on the dense core vesicles in undifferentiated and nerve growth factor-differentiated PC12 cells. Our results indicate that endogenous RalA and RalB function specifically as GTP sensors for the GTP-dependent exocytosis of dense core vesicles, but they are not required for the general secretory pathways, including tethering of vesicles to the plasma membrane and Ca 2+ -dependent exocytosis.
Materialart:
Online-Ressource
ISSN:
0270-6474
,
1529-2401
DOI:
10.1523/JNEUROSCI.2537-06.2007
Sprache:
Englisch
Verlag:
Society for Neuroscience
Publikationsdatum:
2007
ZDB Id:
1475274-8
SSG:
12
