Better explicating the strengths and shortcomings of these models will help refine projections and improve transparency in the years ahead.
Image credit: Witsawat.S.
Edited by Mu-ming Poo, University of California, Berkeley, CA, and approved July 16, 2013 (received for review January 25, 2013)
Abstract
Atypical protein kinase C (aPKC) isoforms ζ and λ interact with polarity complex protein Par3 and are evolutionarily conserved regulators of cell polarity. Prkcz encodes aPKC-ζ and PKM-ζ, a truncated, neuron-specific alternative transcript, and Prkcl encodes aPKC-λ. Here we show that, in embryonic hippocampal neurons, two aPKC isoforms, aPKC-λ and PKM-ζ, are expressed. The localization of these isoforms is spatially distinct in a polarized neuron. aPKC-λ, as well as Par3, localizes at the presumptive axon, whereas PKM-ζ and Par3 are distributed at non-axon-forming neurites. PKM-ζ competes with aPKC-λ for binding to Par3 and disrupts the aPKC-λ–Par3 complex. Silencing of PKM-ζ or overexpression of aPKC-λ in hippocampal neurons alters neuronal polarity, resulting in neurons with supernumerary axons. In contrast, the overexpression of PKM-ζ prevents axon specification. Our studies suggest a molecular model wherein mutually antagonistic intermolecular competition between aPKC isoforms directs the establishment of neuronal polarity.
Footnotes
- ↵1To whom correspondence may be addressed. E-mail: sourav.ghosh{at}arizona.edu or tjprice{at}u.arizona.edu.
Author contributions: S.S.P., T.J.P., and S.G. designed research; S.S.P., E.K.M., S.M.H., I.Y.M., J.K.M., and K.M.G. performed research; S.S.P., E.K.M., S.M.H., Y.K., J.-Y.K., P.A.S.J., J.M.W., K.M.G., T.J.P., and S.G. analyzed data; and S.S.P., E.K.M., S.M.H., T.J.P., and S.G. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1301588110/-/DCSupplemental.
aPKC isoforms in neuronal polarity
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