Type I PIP5Kα negatively regulates NGF-induced neurite outgrowth in PC12 cells
PC12 세포에서 NGF에 의한 neurite outgrowth에 미치는 PIP5KIa의 저해 작용
"Type I phosphatidylinositol 4-phosphate 5-kinase (PIP5KI) is responsible for the production of a membrane lipid, phosphatidylinositol 4,5-bisphosphate (PtdIns[4,5]P2). Here, I have examined whether PIP5KIα, an isoform of PIP5Kα, plays a role in neurite outgrowth. For this, I generated a stable PC12 cell line lacking PIP5KIa by microRNA (miRNA) expression, leading to decreased PtdIns(4,5)P2 level. Results show that neurite outgrowth induced by nerve growth factor (NGF) was more prominent in PIP5KIa-deficient cells than in control miRNA-expressing cells. Reintroduction of PIP5KIα into the PIP5KIα-deficient cells attenuated NGF-induced neurite outgrowth. Similar to the neurite changes, PIP5KIα deficiency promoted NGF-induced Akt phosphorylation that was reversed by the PIP5KIα reintroduction. Treatment of exogenous PtdIns(4,5)P2 also inhibited Akt phosphorylation by NGF. Together, these results suggest that PIP5KIα-driven PtdIns[4,5]P2 acts as a negative regulator of neurite outgrowth by modulating Akt activity.
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