Expression of PKC Iota Affects Neuronal Differentiation of PC12 Cells at Least Partly Independent of Kinase Function

• 作者: Alan R. Schoenfeld Alana Doonachar
• 来源期刊: 细胞生物学(英文)
• 学科: 医学
• 关键词: ATYPICAL PKC NEURITE OUTGROWTH Neuronal Differentiation NEUROENDOCRINE PC12 PKC Iota
• 年，卷（期）: 2014,（1）
• 页码范围: 1-13
• 页数: 13页
• 分类号: R73

摘要

Atypical PKC (aPKC) plays a role in establishing cell polarity and has been indicated in neuronal differentiation and polarization, including neurite formation in rat pheochromocytoma PC12 cells, albeit by unclear mechanisms. Here, the role of the aPKC isoform, PKC iota (PKCι), in the early neuronal differentiation of PC12 cells, was investigated. NGF-treated PC12 cells with stably expressed exogenous wild-type PKCι showed decreased expression of a neuroendocrine marker, increased expression of a neuronal marker and increased neurite formation. Stable expression of a kinase-inactive PKCι, but not constitutively active PKCι lacking a regulatory domain, had similar though less potent effects. Pharmacological inhibition of endogenous aPKC kinase activity in parental PC12 cells did not inhibit neurite formation, suggesting that some of the observed effects of PKCι expression on neuronal differentiation are kinase-independent. Interestingly, exogenous expression of wild-type and kinase-inactive PKCι had little effect on overall PKCι activity, but caused a decrease in PKC zeta (PKCζ) kinase activity, suggesting an interplay between the two isoforms that may underlie the observed results. Overall, these findings suggest that in PC12 and perhaps other neuroendocrine precursor cells, PKCι influences an early differentiation decision between the neuroendocrine (chromaffin) and sympathetic neuron cell lineages, potentially by affecting PKCζ function.