Phosphatidylinositol 4-phosphate 5-kinase ? negatively regulates nerve growth factor-induced neurite outgrowth in PC12 cells.

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 PIP5K?, an isoform of PIP5K, could have a role in neurite outgrowth induced by nerve growth factor (NGF). For this purpose, we knocked down PIP5K? in PC12 rat pheochromocytoma cells by stable expression of PIP5K? microRNA that significantly reduced PIP5K? expression and PIP2 level. Interestingly, NGF-induced neurite outgrowth was more prominent in PIP5K?-knockdown (KD) cells than in control cells. Conversely, add-back of PIP5K? into PIP5K? 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 PIP5K? KD, but was attenuated by the reintroduction of PIP5K?. Moreover, exogenously applied PIP2 to PIP5K? KD cells also suppressed Akt activation by NGF. Together, our results suggest that PIP5K? acts as a negative regulator of NGF-induced neurite outgrowth by inhibiting PI3K/Akt signaling pathway in PC12 cells.

SUBMITTER: Liu T 

PROVIDER: S-EPMC3641393 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature