mTORC1 is involved in DGKβ-induced neurite outgrowth and spinogenesis

Abstract

Diacylglycerol kinase β (DGKβ) is an enzyme converting DG to phosphatidic acid (PA) and is specifically expressed in neurons, especially those in the cerebral cortex, hippocampus and striatum. We previously reported that DGKβ induces neurite outgrowth and spinogenesis, contributing to higher brain function including emotion and memory, and plasma membrane localization of DGKβ via the C1 domain and a cluster of basic amino acids at the C-terminus is necessary for its function. To clarify the mechanisms involved in neuronal development by DGKβ, we investigated whether DGKβ activity induces neurite outgrowth using human neuroblastoma SH-SY5Y cells. DGKβ induced neurite outgrowth by activation of mammalian target of rapamycin complex 1 (mTORC1) through a kinase-dependent pathway. In addition, in primary cultured cortical and hippocampal neurons, inhibition of mTORC1 abolished DGKβ induced-neurite outgrowth, branching and spinogenesis. These results indicated that DGKβ induces neurite outgrowth and spinogenesis by activating mTORC1 in a kinase-dependent pathway.

Keywords: Diacylglycerol kinase; Mammalian target of rapamycin; Neurite; Phosphatidic acid; Spinogenesis.