Copine1 is a ubiquitously expressed protein found in various tissues including the brain, but little is known about the physiological function of this protein. Here, we showed that copine1 is involved in neuronal differentiation. Over-expression of copine1 clearly increased neurite outgrowth and expression of Tuj1, a neuronal marker protein, in HiB5 cells. In addition, endogenous copine1 was transiently increased at the early time during neuronal differentiation of HiB5 cells. When the expression of endogenous copine1 was knocked-down by its specific shRNA, PDGF-mediated neurite outgrowth was clearly decreased in HiB5 cells. Furthermore, over-expression of copine1 increased phosphorylation of Akt and copine1-specific shRNA de-creased phosphorylation of Akt during neuronal differen-tiation of HiB5 cells. Interestingly, the phosphorylation level of PI3K, generally known as an upstream protein of Akt, was not changed by copine1 expression. These re-sults suggest that copine1 enhances neuronal differentiation of HiB5 cells not through the PI3K-Akt pathway, but by using another Akt activated signal pathway.

Keywords: Akt, copine1, HiB5 cell, neuronal differentiation