Garcia E P, Mehta S, Blair L A, Wells D G, Shang J, Fukushima T, Fallon J R, Garner C C, Marshall J
Department of Molecular Pharmacology, Physiology, and Biotechnology, Brown University, Providence, Rhode Island 02912, USA.
Neuron. 1998 Oct;21(4):727-39. doi: 10.1016/s0896-6273(00)80590-5.
The mechanism of kainate receptor targeting and clustering is still unresolved. Here, we demonstrate that members of the SAP90/PSD-95 family colocalize and associate with kainate receptors. SAP90 and SAP102 coimmunoprecipitate with both KA2 and GluR6, but only SAP97 coimmunoprecipitates with GluR6. Similar to NMDA receptors, GluR6 clustering is mediated by the interaction of its C-terminal amino acid sequence, ETMA, with the PDZ1 domain of SAP90. In contrast, the KA2 C-terminal region binds to, and is clustered by, the SH3 and GK domains of SAP90. Finally, we show that SAP90 coexpressed with GluR6 or GluR6/KA2 receptors alters receptor function by reducing desensitization. These studies suggest that the organization and electrophysiological properties of synaptic kainate receptors are modified by association with members of the SAP90/PSD-95 family.
红藻氨酸受体靶向和聚集的机制仍未得到解决。在此，我们证明了SAP90/PSD - 95家族成员与红藻氨酸受体共定位并相互关联。SAP90和SAP102与KA2和GluR6都能进行共免疫沉淀，但只有SAP97能与GluR6进行共免疫沉淀。与NMDA受体类似，GluR6的聚集是由其C末端氨基酸序列ETMA与SAP90的PDZ1结构域相互作用介导的。相比之下，KA2的C末端区域与SAP90的SH3和GK结构域结合并由其聚集。最后，我们表明与GluR6或GluR6/KA2受体共表达的SAP90通过减少脱敏来改变受体功能。这些研究表明，突触红藻氨酸受体的组织和电生理特性通过与SAP90/PSD - 95家族成员的关联而得到修饰。
