Competing molecular interactions of aPKC isoforms regulate neuronal polarity.

ABSTRACT: Atypical protein kinase C (aPKC) isoforms ? and ? interact with polarity complex protein Par3 and are evolutionarily conserved regulators of cell polarity. Prkcz encodes aPKC-? and PKM-?, a truncated, neuron-specific alternative transcript, and Prkcl encodes aPKC-?. Here we show that, in embryonic hippocampal neurons, two aPKC isoforms, aPKC-? and PKM-?, are expressed. The localization of these isoforms is spatially distinct in a polarized neuron. aPKC-?, as well as Par3, localizes at the presumptive axon, whereas PKM-? and Par3 are distributed at non-axon-forming neurites. PKM-? competes with aPKC-? for binding to Par3 and disrupts the aPKC-?-Par3 complex. Silencing of PKM-? or overexpression of aPKC-? in hippocampal neurons alters neuronal polarity, resulting in neurons with supernumerary axons. In contrast, the overexpression of PKM-? prevents axon specification. Our studies suggest a molecular model wherein mutually antagonistic intermolecular competition between aPKC isoforms directs the establishment of neuronal polarity.

SUBMITTER: Parker SS 

PROVIDER: S-EPMC3761571 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature