Competing molecular interactions of aPKC isoforms regulate neuronal polarity.
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.
Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ 85724, USA.
Sara S
SS
Parker
Edward K
EK
Mandell
Sophie M
SM
Hapak
Irina Y
IY
Maskaykina
Yael
Y
Kusne
Ji-Young
JY
Kim
Jamie K
JK
Moy
Paul A
PA
St John
Jean M
JM
Wilson
Katalin M
KM
Gothard
Theodore J
TJ
Price
Sourav
S
Ghosh
D000818:Animals; D016764:Cell Polarity / Q000502:physiology*; D002478:Cells, Cultured; D005260:Female; D006624:Hippocampus / Q000166:cytology*; D007527:Isoenzymes / Q000378:metabolism* / Q000502:physiology; D009474:Neurons / Q000166:cytology*; D011247:Pregnancy; D011493:Protein Kinase C / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D007527:Isoenzymes; D011493:Protein Kinase C
axonogenesis; neurodevelopment; symmetry breaking