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Proc Natl Acad Sci U S A. 2013 Aug 27;110(35):14450-5. doi: 10.1073/pnas.1301588110. Epub 2013 Aug 12.

Competing molecular interactions of aPKC isoforms regulate neuronal polarity.

Author information

1
Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ 85724, USA.

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.

KEYWORDS:

axonogenesis; neurodevelopment; symmetry breaking

PMID:
23940317
PMCID:
PMC3761571
DOI:
10.1073/pnas.1301588110
[Indexed for MEDLINE]
Free PMC Article
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