Friedman Lauren G, Benson Deanna L, Huntley George W
Fishberg Department of Neuroscience, Friedman Brain Institute and the Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, USA.
Fishberg Department of Neuroscience, Friedman Brain Institute and the Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, USA.
Curr Top Dev Biol. 2015;112:415-65. doi: 10.1016/bs.ctdb.2014.11.025. Epub 2015 Feb 11.
It is tacitly understood that cell adhesion molecules (CAMs) are critically important for the development of cells, circuits, and synapses in the brain. What is less clear is what CAMs continue to contribute to brain structure and function after the early period of development. Here, we focus on the cadherin family of CAMs to first briefly recap their multidimensional roles in neural development and then to highlight emerging data showing that with maturity, cadherins become largely dispensible for maintaining neuronal and synaptic structure, instead displaying new and narrower roles at mature synapses where they critically regulate dynamic aspects of synaptic signaling, structural plasticity, and cognitive function. At mature synapses, cadherins are an integral component of multiprotein networks, modifying synaptic signaling, morphology, and plasticity through collaborative interactions with other CAM family members as well as a variety of neurotransmitter receptors, scaffolding proteins, and other effector molecules. Such recognition of the ever-evolving functions of synaptic cadherins may yield insight into the pathophysiology of brain disorders in which cadherins have been implicated and that manifest at different times of life.
人们默认细胞黏附分子（CAMs）对大脑中细胞、神经回路和突触的发育至关重要。尚不清楚的是，在发育早期之后，细胞黏附分子对大脑结构和功能还会持续发挥哪些作用。在这里，我们聚焦于细胞黏附分子中的钙黏蛋白家族，首先简要回顾它们在神经发育中的多维度作用，然后强调新出现的数据，这些数据表明，随着成熟，钙黏蛋白在很大程度上对于维持神经元和突触结构不再是必需的，而是在成熟突触中发挥新的、更窄的作用，在那里它们严格调控突触信号传导、结构可塑性和认知功能的动态方面。在成熟突触中，钙黏蛋白是多蛋白网络的一个组成部分，通过与其他细胞黏附分子家族成员以及多种神经递质受体、支架蛋白和其他效应分子的协同相互作用，修饰突触信号传导、形态和可塑性。对突触钙黏蛋白不断演变的功能的这种认识，可能有助于深入了解与钙黏蛋白有关且在生命不同时期出现的脑部疾病的病理生理学。
