Department of Psychology, Dalian Medical University, Dalian, Liaoning Province, China
Departments of Ophthalmology, Developmental Biology, and Microbiology & Molecular Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania
J Neurosci. 2022 Jun 15;42(24):4774-4793. doi: 10.1523/JNEUROSCI.0059-22.2022.
Normal neural circuits and functions depend on proper neuronal differentiation, migration, synaptic plasticity, and maintenance. Abnormalities in these processes underlie various neurodevelopmental, neuropsychiatric, and neurodegenerative disorders. Neural development and maintenance are regulated by many proteins. Among them are Par3, Par6 (partitioning defective 3 and 6), and aPKC (atypical protein kinase C) families of evolutionarily conserved polarity proteins. These proteins perform versatile functions by forming tripartite or other combinations of protein complexes, which hereafter are collectively referred to as "Par complexes." In this review, we summarize the major findings on their biophysical and biochemical properties in cell polarization and signaling pathways. We next summarize their expression and localization in the nervous system as well as their versatile functions in various aspects of neurodevelopment, including neuroepithelial polarity, neurogenesis, neuronal migration, neurite differentiation, synaptic plasticity, and memory. These versatile functions rely on the fundamental roles of Par complexes in cell polarity in distinct cellular contexts. We also discuss how cell polarization may correlate with subcellular polarization in neurons. Finally, we review the involvement of Par complexes in neuropsychiatric and neurodegenerative disorders, such as schizophrenia and Alzheimer's disease. While emerging evidence indicates that Par complexes are essential for proper neural development and maintenance, many questions on their functions have yet to be answered. Thus, Par3, Par6, and aPKC continue to be important research topics to advance neuroscience.
正常的神经回路和功能依赖于适当的神经元分化、迁移、突触可塑性和维持。这些过程中的异常是各种神经发育、神经精神和神经退行性疾病的基础。神经发育和维持受到许多蛋白质的调节。其中包括 Par3、Par6（分区缺陷 3 和 6）和 aPKC（非典型蛋白激酶 C）家族的进化保守极性蛋白。这些蛋白质通过形成三联体或其他蛋白复合物组合来执行多种功能，以下统称为“Par 复合物”。在这篇综述中，我们总结了它们在细胞极化和信号通路中的生物物理和生化特性的主要发现。接下来，我们总结了它们在神经系统中的表达和定位，以及它们在神经发育的各个方面的多功能性，包括神经上皮极性、神经发生、神经元迁移、突起分化、突触可塑性和记忆。这些多功能性依赖于 Par 复合物在不同细胞环境中细胞极性的基本作用。我们还讨论了细胞极化如何与神经元中的亚细胞极化相关。最后，我们综述了 Par 复合物在神经精神和神经退行性疾病中的作用，如精神分裂症和阿尔茨海默病。尽管有新的证据表明 Par 复合物对正常的神经发育和维持至关重要，但它们的许多功能仍有待解答。因此，Par3、Par6 和 aPKC 仍然是推进神经科学的重要研究课题。
