TITLE:
Expression of PKC Iota Affects Neuronal Differentiation of PC12 Cells at Least Partly Independent of Kinase Function
AUTHORS:
Alana Doonachar, Alan R. Schoenfeld
KEYWORDS:
Atypical PKC; Neurite Outgrowth; Neuronal Differentiation; Neuroendocrine; PC12; PKC Iota
JOURNAL NAME:
CellBio,
Vol.3 No.1,
February
28,
2014
ABSTRACT: 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.