Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ 85724, USA.
Proc Natl Acad Sci U S A. 2013 Aug 27;110(35):14450-5. doi: 10.1073/pnas.1301588110. Epub 2013 Aug 12.
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.
非典型蛋白激酶 C（aPKC）同工型 ζ 和 λ 与极性复合物蛋白 Par3 相互作用，是细胞极性的进化保守调节剂。Prkcz 编码 aPKC-ζ 和 PKM-ζ，一种截断的、神经元特异性的替代转录本，而 Prkcl 编码 aPKC-λ。在这里，我们表明在胚胎海马神经元中表达两种 aPKC 同工型，aPKC-λ 和 PKM-ζ。这些同工型在极化神经元中的定位是空间上不同的。aPKC-λ 与 Par3 一起定位在假定的轴突上，而 PKM-ζ 和 Par3 分布在不形成轴突的神经突上。PKM-ζ 与 aPKC-λ 竞争结合 Par3 并破坏 aPKC-λ-Par3 复合物。海马神经元中 PKM-ζ 的沉默或 aPKC-λ 的过表达会改变神经元极性，导致神经元产生过多的轴突。相比之下，PKM-ζ 的过表达可防止轴突特化。我们的研究提出了一个分子模型，其中 aPKC 同工型之间相互拮抗的分子间竞争指导神经元极性的建立。
