A novel family of adhesion-like molecules that interacts with the NMDA receptor
A novel family of adhesion-like molecules that interacts with the NMDA receptor
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DOI：
10.1523/jneurosci.3799-05.2006
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发表时间：
2006-02-22
影响因子：
5.3
通讯作者：
Wenthold, RJ
中科院分区：
文献类型：
--
作者：
Wang, CY;Chang, K;Wenthold, RJ
我们发现了一类新的突触粘附样分子(SALM)家族。家族成员SALM1-SALM4具有单一的跨膜(TM)结构域，包含细胞外富含亮氨酸的重复序列、Ig C2类型域、纤维连接蛋白III型结构域和细胞内突触后密度-95(PSD-95)/Discs Large/Zona occludens-1(PDZ)结合结构域，除SALM4外，所有成员都存在该结构域。SALM1与PSD-95、突触相关蛋白102(SAP102)和SAP97通过洗涤剂溶解的脑的免疫共沉淀相互作用。分布研究表明，SALM1存在于突触膜和突触后密度组分，但也存在于轴突和树突。SALM1基因转染海马神经元4d后，48h后神经元的树突长度增加一倍以上，而14DIV基因对神经元突起生长无明显影响。SALM1在14个DIV神经元中的过表达使NMDA受体(NR)和PSD-95向树突点募集。这一效应依赖于SALM1的PDZ结合域。SALM1还能增强NR2A亚单位的表面表达。抗SALM1抗体与洗涤剂溶解的脑膜的免疫共沉淀显示NR1和NR2亚单位的免疫共沉淀。将NR1和NR2的cDNAs导入异种细胞后，通过免疫共沉淀分析，我们发现SALM1也通过其胞外或TM1结构域与NMDA受体NR1亚基相互作用。
We have identified a novel family of synaptic adhesion-like molecules (SALMs). The family members, SALM1-SALM4, have a single transmembrane (TM) domain and contain extracellular leucine-rich repeats, an Ig C2 type domain, a fibronectin type III domain, and an intracellular postsynaptic density-95 (PSD-95)/Discs large/ zona occludens-1 (PDZ) binding domain, which is present on all members except SALM4. SALM1 interacts with PSD-95, synapse-associated protein 102 (SAP102), and SAP97 based on coimmunoprecipitation of detergent-solubilized brain. Distribution studies show that SALM1 is present in synaptic membrane and postsynaptic density fractions but is also distributed in axons and dendrites. Transfection of hippocampal neurons for 4 d in vitro (DIV) with SALM1 more than doubles the dendritic lengths of neurons after 48 h, whereas transfection of neurons 14 DIV has no significant effect on neurite outgrowth. Overexpression of SALM1 in 14 DIV neurons recruits NMDA receptors (NR) and PSD-95 to dendritic puncta. This effect is dependent on the PDZ-binding domain of SALM1. SALM1 also enhances surface expression of transfected NR2A subunit. Immunoprecipitation of detergent-solubilized brain membranes with anti-SALM1 antibodies shows coimmunoprecipitation of NR1 and NR2 subunits. After transfection of heterologous cells with NR1 and NR2 cDNAs, through coimmunoprecipitation analyses, we find that SALM1 also interacts with the NMDA receptor NR1 subunit through its extracellular or TM1 domains.