美国加州大学戴维斯分校网站近日报道称,该校研究人员最近发现了一种名为SynDIG1的新型脑蛋白,对突触的形成和发育起着至关重要的作用。报道称,这一发现将增进对人类认知能力和大脑功能紊乱病症的理解,为自闭症、精神分裂症等疾病的治疗带来新希望。相关研究成果发表在1月14日的《神经元》杂志上。
突触是一种复杂的化学信号系统,负责神经细胞间的沟通,对于学习、记忆、认知等具有重要作用。突触失衡会造成脑功能紊乱,导致罹患自闭症、精神分裂等疾病。大脑中绝大多数的突触将谷氨酸作为一种神经递质使用。过去的研究显示,调控谷氨酸受体(AMPA受体),对于神经细胞间的交流至关重要。
加州大学戴维斯分校的药理学助理教授埃尔娃·迪亚兹带领一研究小组,通过对一种预测基因(tmem90b)的分析,发现了一种新型跨膜蛋白,将其命名为SynDIG1(突触分化诱导基因产物)。在分子神经生物学家和电生理学家的帮助下,他们从老鼠的海马体神经元中分离出细胞,进行一系列的测试,以了解该蛋白的功能。
测试表明,SynDIG1和AMPA受体会在突触的形成位点同时存在,这表明该种蛋白在突触形成的早期阶段是必要的;研究还发现,通过操控神经细胞中的SynDIG1表达水平,会改变突触的数量和质量:减少SynDIG1表达,突触会愈加小而少;若增强SynDIG1表达,突触则会更加成熟、稳定。这表明,SynDIG1对突触形成、发育以及寿命等有着至关重要的作用。
迪亚兹认为,SynDIG1对新老神经细胞同样重要,其会影响神经发育,与某些神经疾病有重要关联,或许将来许多大脑疾病可被重新定义为突触疾病。下一步,研究人员将在活体老鼠身上测试SynDIG1的作用。(生物谷Bioon.com)
生物谷推荐原始出处:
Neuron, Volume 65, Issue 1, 80-93, 14 January 2010 | 10.1016/j.neuron.2009.12.021
SynDIG1: An Activity-Regulated, AMPA- Receptor-Interacting Transmembrane Protein that Regulates Excitatory Synapse Development
Evgenia Kalashnikova, Ramón A. Lorca, Inderpreet Kaur, Gustavo A. Barisone, Bonnie Li, Tatsuto Ishimaru, James S. Trimmer, Durga P. Mohapatra, Elva Díaz
During development of the central nervous system, precise synaptic connections between presynaptic and postsynaptic neurons are formed. While significant progress has been made in our understanding of AMPA receptor trafficking during synaptic plasticity, less is known about the molecules that recruit AMPA receptors to nascent synapses during synaptogenesis. Here we identify a type II transmembrane protein (SynDIG1) that regulates AMPA receptor content at developing synapses in dissociated rat hippocampal neurons. SynDIG1 colocalizes with AMPA receptors at synapses and at extrasynaptic sites and associates with AMPA receptors in heterologous cells and brain. Altered levels of SynDIG1 in cultured neurons result in striking changes in excitatory synapse number and function. SynDIG1-mediated synapse development is dependent on association with AMPA receptors via its extracellular C terminus. Intriguingly, SynDIG1 content in dendritic spines is regulated by neuronal activity. Altogether, we define SynDIG1 as an activity-regulated transmembrane protein that regulates excitatory synapse development.