Phosphatidylinositol 4-phosphate 5-kinase alpha negatively regulates nerve growth factor-induced neurite outgrowth in PC12 cells
Experimental & Molecular Medicine
;
: e16-2013.
Artículo
en Inglés
| WPRIM
| ID: wpr-165480
ABSTRACT
Neurite outgrowth, a cell differentiation process involving membrane morphological changes, is critical for neuronal network and development. The membrane lipid, phosphatidylinositol (PI) 4,5-bisphosphate (PIP2), is a key regulator of many important cell surface events of membrane signaling, trafficking and dynamics. This lipid is produced mainly by the type I PI 4-phosphate 5-kinase (PIP5K) family members. In this study, we addressed whether PIP5Kalpha, an isoform of PIP5K, could have a role in neurite outgrowth induced by nerve growth factor (NGF). For this purpose, we knocked down PIP5Kalpha in PC12 rat pheochromocytoma cells by stable expression of PIP5Kalpha microRNA that significantly reduced PIP5Kalpha expression and PIP2 level. Interestingly, NGF-induced neurite outgrowth was more prominent in PIP5Kalpha-knockdown (KD) cells than in control cells. Conversely, add-back of PIP5Kalpha into PIP5Kalpha KD cells abrogated the effect of NGF on neurite outgrowth. NGF treatment activated PI 3-kinase (PI3K)/Akt pathway, which seemed to be associated with reactive oxygen species generation. Similar to the changes in neurite outgrowth, the PI3K/Akt activation by NGF was potentiated by PIP5Kalpha KD, but was attenuated by the reintroduction of PIP5Kalpha. Moreover, exogenously applied PIP2 to PIP5Kalpha KD cells also suppressed Akt activation by NGF. Together, our results suggest that PIP5Kalpha acts as a negative regulator of NGF-induced neurite outgrowth by inhibiting PI3K/Akt signaling pathway in PC12 cells.
Texto completo:
Disponible
Índice:
WPRIM (Pacífico Occidental)
Asunto principal:
Fosforilación
/
Transducción de Señal
/
Células PC12
/
Neuritas
/
Especies Reactivas de Oxígeno
/
Fosfotransferasas (Aceptor de Grupo Alcohol)
/
Fosfatidilinositol 4,5-Difosfato
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Fosfatidilinositol 3-Quinasas
/
Factor de Crecimiento Nervioso
/
Activación Enzimática
Límite:
Animales
Idioma:
Inglés
Revista:
Experimental & Molecular Medicine
Año:
2013
Tipo del documento:
Artículo
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