Two distinct regulatory mechanisms of neurotransmitter release by phosphatidylinositol 3-kinase.
J Neurochem
; 94(2): 502-9, 2005 Jul.
Article
en En
| MEDLINE
| ID: mdl-15998300
ABSTRACT
Recent studies have indicated that various growth factors are involved in synaptic functions; however, the precise mechanisms remain unclear. In order to elucidate the molecular mechanisms of the growth factor-mediated regulation of presynaptic functions, the effects of epidermal growth factor (EGF) and insulin-like growth factor-1 (IGF-1) on neurotransmitter release were studied in rat PC12 cells. Brief treatment with EGF and IGF-1 enhanced Ca2+-dependent dopamine release in a concentration-dependent manner. EGF activated both mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3-kinase) pathways, and the EGF-dependent enhancement of DA release was suppressed by a MAPK kinase inhibitor as well as by PI3-kinase inhibitors. In striking contrast, IGF-1 activated the PI3-kinase pathway but not the MAPK pathway, and IGF-1-dependent enhancement was suppressed by a PI3-kinase inhibitor but not by a MAPK kinase inhibitor. The enhanced green fluorescent protein-tagged pleckstrin homology (PH) domain of protein kinase B, which selectively binds to phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol 3,4,5-triphosphate, was translocated to the plasma membrane after treatment with either EGF or NGF. By contrast, no significant redistribution was induced by IGF-1. These results indicate that PI3-kinase participates in the enhancement of neurotransmitter release by two distinct mechanisms EGF and NGF activate PI3-kinase in the plasma membrane, whereas IGF-1 activates PI3-kinase possibly in the intracellular membrane, leading to enhancement of neurotransmitter release in a MAPK-dependent and -independent manner respectively.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Dopamina
/
Membrana Celular
/
Fosfatidilinositol 3-Quinasas
/
Espacio Extracelular
Límite:
Animals
Idioma:
En
Revista:
J Neurochem
Año:
2005
Tipo del documento:
Article