Clifton Nicholas E, Trent Simon, Thomas Kerrie L, Hall Jeremy
Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, United Kingdom.
MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, United Kingdom.
Mol Neuropsychiatry. 2019 Jun;5(3):147-161. doi: 10.1159/000500267. Epub 2019 May 23.
Alterations in synaptic signaling and plasticity occur during the refinement of neural circuits over the course of development and the adult processes of learning and memory. Synaptic plasticity requires the rearrangement of protein complexes in the postsynaptic density (PSD), trafficking of receptors and ion channels and the synthesis of new proteins. Activity-induced short Homer proteins, Homer1a and Ania-3, are recruited to active excitatory synapses, where they act as dominant negative regulators of constitutively expressed, longer Homer isoforms. The expression of Homer1a and Ania-3 initiates critical processes of PSD remodeling, the modulation of glutamate receptor-mediated functions, and the regulation of calcium signaling. Together, available data support the view that Homer1a and Ania-3 are responsible for the selective, transient destabilization of postsynaptic signaling complexes to facilitate plasticity of the excitatory synapse. The interruption of activity-dependent Homer proteins disrupts disease-relevant processes and leads to memory impairments, reflecting their likely contribution to neurological disorders.
在神经回路发育过程以及成体学习和记忆过程的精细化阶段，突触信号传导和可塑性会发生改变。突触可塑性需要突触后致密区（PSD）中蛋白质复合物的重排、受体和离子通道的运输以及新蛋白质的合成。活性诱导的短型荷马蛋白Homer1a和Ania-3被招募到活跃的兴奋性突触，在那里它们作为组成型表达的较长荷马异构体的显性负调控因子发挥作用。Homer1a和Ania-3的表达启动了PSD重塑、谷氨酸受体介导功能的调节以及钙信号传导调节的关键过程。总体而言，现有数据支持这样的观点，即Homer1a和Ania-3负责突触后信号复合物的选择性、短暂性不稳定，以促进兴奋性突触的可塑性。依赖活性的荷马蛋白的中断会破坏与疾病相关的过程并导致记忆障碍，这反映了它们可能对神经疾病有影响。
