SAP97 is associated with the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor GluR1 subunit.
SAP97 is associated with the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor GluR1 subunit.
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发表时间：
1998
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通讯作者：
A. Leonard;M. Davare;M. C. Horne;C. C. Garner-C.;J. W. Hell
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作者：
A. Leonard;M. Davare;M. C. Horne;C. C. Garner-C.;J. W. Hell
快速的谷氨酸能突触传递是由离子型谷氨酸受体介导的，并依赖于它们在突触后膜上的精确定位，与突触前神经递质释放位点相反。N-甲基-D-天冬氨酸型谷氨酸受体的突触后定位可由突触相关蛋白（SAP）SAP90、SAP102和chapsyn-110介导。SAP含有三个PDZ结构域，其可以与蛋白质的C末端相互作用，例如N-甲基-D-天冬氨酸受体亚基，其在-2位携带丝氨酸或苏氨酸，在C末端（位置0）携带缬氨酸、异亮氨酸或亮氨酸。我们现在表明，SAP 97，其在突触的功能还不清楚，是与α-氨基-3-羟基-5-甲基异恶唑-4-丙酸（AMPA）型谷氨酸受体。AMPA受体可能是四聚体，由四个AMPA受体亚基GluR1 - 4中的两个或更多个形成。GluR1具有与SAP的PDZ结构域相互作用的C-末端共有序列。SAP97存在于从大鼠脑的洗涤剂提取物免疫沉淀的AMPA受体复合物中。用交联剂二硫代双（琥珀酰亚胺基丙酸酯）和十二烷基硫酸钠增溶处理大鼠脑膜组分后，SAP 97与GluR1相关，但不与GluR2或GluR3相关。重组蛋白的体外实验表明，SAP 97特异性地与GluR1的C末端结合，但不与其他AMPA受体亚基结合。我们的研究结果表明，SAP 97可能参与本地化AMPA受体在突触后位点，通过其与GluR1亚基的相互作用。
Rapid glutamatergic synaptic transmission is mediated by ionotropic glutamate receptors and depends on their precise localization at postsynaptic membranes opposing the presynaptic neurotransmitter release sites. Postsynaptic localization of N-methyl-D-aspartate-type glutamate receptors may be mediated by the synapse-associated proteins (SAPs) SAP90, SAP102, and chapsyn-110. SAPs contain three PDZ domains that can interact with the C termini of proteins such as N-methyl-D-aspartate receptor subunits that carry a serine or threonine at the -2 position and a valine, isoleucine, or leucine at the very C terminus (position 0). We now show that SAP97, a SAP whose function at the synapse has been unclear, is associated with alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-type glutamate receptors. AMPA receptors are probably tetramers and are formed by two or more of the four AMPA receptor subunits GluR1-4. GluR1 possesses a C-terminal consensus sequence for interactions with PDZ domains of SAPs. SAP97 was present in AMPA receptor complexes immunoprecipitated from detergent extracts of rat brain. After treatment of rat brain membrane fractions with the cross-linker dithiobis(succinimidylpropionate) and solubilization with sodium dodecylsulfate, SAP97 was associated with GluR1 but not GluR2 or GluR3. In vitro experiments with recombinant proteins indicate that SAP97 specifically associates with the C terminus of GluR1 but not other AMPA receptor subunits. Our findings suggest that SAP97 may be involved in localizing AMPA receptors at postsynaptic sites through its interaction with the GluR1 subunit.