Department of Physiology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Cytoskeleton (Hoboken). 2012 Jul;69(7):426-41. doi: 10.1002/cm.21015. Epub 2012 Mar 12.
Dendritic spines are the sites of most excitatory synapses in the central nervous system. Recent studies have shown that spines function independently of each other, and they are currently the smallest known processing units in the brain. Spines exist in an array of morphologies, and spine structure helps dictate synaptic function. Dendritic spines are rich in actin, and actin rearrangements are critical regulators of spine morphology and density. In this review, we discuss the importance of actin in regulating dendritic spine morphogenesis, and discuss the upstream signal transduction pathways that either foster or inhibit actin polymerization. The understanding of actin regulatory pathways is best conceptualized as a hierarchical network in which molecules function in discrete levels defined by their molecular distance to actin. To this end, we focus on several classes of molecules, including guanine nucleotide exchange factors, small GTPases, small GTPase effectors, and actin binding proteins. We discuss how individual proteins in these molecular classes impact spine morphogenesis, and reveal the biochemical interactions in these networks that are responsible for shaping actin polymerization. Finally, we discuss the importance of these actin regulatory pathways in neuropsychiatric disorders.
树突棘是中枢神经系统中大多数兴奋性突触的部位。最近的研究表明，棘突彼此独立地发挥作用，它们是目前已知的大脑中最小的处理单元。棘突存在于多种形态中，棘突结构有助于决定突触功能。树突棘富含肌动蛋白，肌动蛋白重排是调节棘突形态和密度的关键调节剂。在这篇综述中，我们讨论了肌动蛋白在调节树突棘形态发生中的重要性，并讨论了促进或抑制肌动蛋白聚合的上游信号转导途径。对肌动蛋白调节途径的理解最好被概念化为一个层次网络，其中分子在与其距肌动蛋白的分子距离定义的离散水平上发挥作用。为此，我们重点介绍了几类分子，包括鸟嘌呤核苷酸交换因子、小 GTPases、小 GTPase 效应物和肌动蛋白结合蛋白。我们讨论了这些分子类别中的单个蛋白质如何影响棘突形态发生，并揭示了负责塑造肌动蛋白聚合的这些网络中的生化相互作用。最后，我们讨论了这些肌动蛋白调节途径在神经精神疾病中的重要性。
