美國(guó)加州大學(xué)戴維斯分校網(wǎng)站近日?qǐng)?bào)道稱(chēng),，該校研究人員最近發(fā)現(xiàn)了一種名為SynDIG1的新型腦蛋白,，對(duì)突觸的形成和發(fā)育起著至關(guān)重要的作用。報(bào)道稱(chēng),，這一發(fā)現(xiàn)將增進(jìn)對(duì)人類(lèi)認(rèn)知能力和大腦功能紊亂病癥的理解，為自閉癥、精神分裂癥等疾病的治療帶來(lái)新希望,。相關(guān)研究成果發(fā)表在1月14日的《神經(jīng)元》雜志上。
突觸是一種復(fù)雜的化學(xué)信號(hào)系統(tǒng),，負(fù)責(zé)神經(jīng)細(xì)胞間的溝通,，對(duì)于學(xué)習(xí)、記憶,、認(rèn)知等具有重要作用,。突觸失衡會(huì)造成腦功能紊亂，導(dǎo)致罹患自閉癥,、精神分裂等疾病,。大腦中絕大多數(shù)的突觸將谷氨酸作為一種神經(jīng)遞質(zhì)使用。過(guò)去的研究顯示,，調(diào)控谷氨酸受體（AMPA受體）,，對(duì)于神經(jīng)細(xì)胞間的交流至關(guān)重要。
加州大學(xué)戴維斯分校的藥理學(xué)助理教授埃爾娃·迪亞茲帶領(lǐng)一研究小組,，通過(guò)對(duì)一種預(yù)測(cè)基因（tmem90b）的分析,，發(fā)現(xiàn)了一種新型跨膜蛋白，將其命名為SynDIG1（突觸分化誘導(dǎo)基因產(chǎn)物）,。在分子神經(jīng)生物學(xué)家和電生理學(xué)家的幫助下,，他們從老鼠的海馬體神經(jīng)元中分離出細(xì)胞，進(jìn)行一系列的測(cè)試,，以了解該蛋白的功能,。
測(cè)試表明，SynDIG1和AMPA受體會(huì)在突觸的形成位點(diǎn)同時(shí)存在,，這表明該種蛋白在突觸形成的早期階段是必要的,；研究還發(fā)現(xiàn)，通過(guò)操控神經(jīng)細(xì)胞中的SynDIG1表達(dá)水平,，會(huì)改變突觸的數(shù)量和質(zhì)量：減少SynDIG1表達(dá),，突觸會(huì)愈加小而少,；若增強(qiáng)SynDIG1表達(dá)，突觸則會(huì)更加成熟,、穩(wěn)定,。這表明，SynDIG1對(duì)突觸形成,、發(fā)育以及壽命等有著至關(guān)重要的作用,。
迪亞茲認(rèn)為，SynDIG1對(duì)新老神經(jīng)細(xì)胞同樣重要,，其會(huì)影響神經(jīng)發(fā)育,，與某些神經(jīng)疾病有重要關(guān)聯(lián)，或許將來(lái)許多大腦疾病可被重新定義為突觸疾病,。下一步,，研究人員將在活體老鼠身上測(cè)試SynDIG1的作用。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
