Competing molecular interactions of aPKC isoforms regulate neuronal polarity

Sara S. Parker, Edward K. Mandell, Sophie M. Hapak, Irina Y. Maskaykina, Yael Kusne, Ji Young Kim, Jamie K. Moy, Paul A St John, Jean Wilson, Katalin M Gothard, Theodore J. Price, Sourav Ghosh

Research output: Contribution to journalArticle

15 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)14450-14455
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number35
DOIs
Publication statusPublished - Aug 27 2013

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Keywords

  • Axonogenesis
  • Neurodevelopment
  • Symmetry breaking

ASJC Scopus subject areas

  • General

Cite this

Parker, S. S., Mandell, E. K., Hapak, S. M., Maskaykina, I. Y., Kusne, Y., Kim, J. Y., ... Ghosh, S. (2013). Competing molecular interactions of aPKC isoforms regulate neuronal polarity. Proceedings of the National Academy of Sciences of the United States of America, 110(35), 14450-14455. https://doi.org/10.1073/pnas.1301588110