Receptor-type PTP-NP inhibition of Dynamin-1 GTPase activity is associated with neuronal depolarization.
Cell Signal
; 18(9): 1439-46, 2006 Sep.
Article
em En
| MEDLINE
| ID: mdl-16413169
ABSTRACT
Dynamin-1 is a GTP-hydrolyzing protein and a key element in the clathrin-mediated endocytosis of secretory granules and neurovesicles at the plasma membrane. The unique receptor-like protein tyrosine phosphatase, PTP-NP/Phogrin/IAR/IA-2, is associated with neuroendocrine secretory granules and is highly expressed in the brain. Here, we show by confocal microscopy and biochemical studies that PTP-NP rapidly associates with Dynamin-1 in a depolarization-dependent manner and regulates Dynamin-1 GTPase activity upon KCl depolarization of rat primary hippocampal neurons. Depolarization of primary neurons induced direct association of PTP-NP with Dynamin-1 within 30 s. This association resulted in significant inhibition of Dynamin-1 GTPase activity (approximately 75% inhibition). Mutation within the phosphatase domain of PTP-NP (PTP-NP(D947A)) abolished the direct interaction of PTP-NP with Dynamin-1 and failed to inhibit Dynamin-1 GTPase activity. To further confirm the endogenous interaction of Dynamin-1 with wild-type PTP-NP, Dynamin-1 was purified biochemically from rat brain and its interaction with purified PTP-NP was analyzed. Highly purified Dynamin-1 specifically associated with wild-type PTP-NP and not with mutated PTP-NP, resulting in significant inhibition (approximately 70%) of Dynamin-1 GTPase activity. This is the first report to suggest a novel function of this unique receptor-type tyrosine phosphatase as a potential regulator of Dynamin-1 GTPase activity upon neuronal depolarization.
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Base de dados:
MEDLINE
Assunto principal:
Autoantígenos
/
Proteínas Tirosina Fosfatases
/
Dinamina I
/
Potenciais da Membrana
/
Proteínas de Membrana
/
Neurônios
Idioma:
En
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Estados Unidos