GSG1L-containing AMPA receptor complexes are defined by their spatiotemporal expression, native interactome and allosteric sites.
GSG1L-containing AMPA receptor complexes are defined by their spatiotemporal expression, native interactome and allosteric sites.
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DOI：
10.1038/s41467-023-42517-7
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发表时间：
2023-10-26
影响因子：
16.6
通讯作者：
Bowie, Derek
中科院分区：
文献类型：
--
作者：
Perozzo, Amanda M.;Schwenk, Jochen;Kamalova, Aichurok;Nakagawa, Terunaga;Fakler, Bernd;Bowie, Derek
跨膜型AMPA受体调节蛋白(TARP)和生殖细胞特异性基因样蛋白(GSG1L)是CRADIN型AMPA受体(AMPAR)的辅助亚基，对谷氨酸能突触的强度和可塑性具有深刻的调控作用。虽然AMPAR-TARP复合体已被广泛研究，但对含有GSG1L的AMPAR的研究较少。在这里，我们发现GSG1L的时空表达、天然相互作用组和变构位点是不同的。GSG1L通常在脑发育后期以区域特异性的方式表达，约占成年期所有AMPAR复合体的5%。虽然GSG1L可以与tarp或cornichons(CNIH)共同组装，但它也作为唯一的辅助亚单位进行组装。出乎意料的是，GSG1L通过激动剂结合域上两个离散的进化保守的位点起作用，在TARP/KGK位点上有弱的变构相互作用来减缓脱敏，而在不同的位点上有更强的相互作用来减缓脱敏恢复。总之，这些区别有助于解释GSG1L的进化历史，以及它如何在谷氨酸能突触中发挥独特的信号作用。TARPS和GSG1L是进化上和结构上相关的AMPA受体辅助亚基，它们的功能因未解决的机制而不同。在这里，两位作者提供了对含有GSG1L的蛋白质复合体的时空表达、组成和功能的见解。
Transmembrane AMPA receptor regulatory proteins (TARPs) and germ cell-specific gene 1-like protein (GSG1L) are claudin-type AMPA receptor (AMPAR) auxiliary subunits that profoundly regulate glutamatergic synapse strength and plasticity. While AMPAR-TARP complexes have been extensively studied, less is known about GSG1L-containing AMPARs. Here, we show that GSG1L’s spatiotemporal expression, native interactome and allosteric sites are distinct. GSG1L generally expresses late during brain development in a region-specific manner, constituting about 5% of all AMPAR complexes in adulthood. While GSG1L can co-assemble with TARPs or cornichons (CNIHs), it also assembles as the sole auxiliary subunit. Unexpectedly, GSG1L acts through two discrete evolutionarily-conserved sites on the agonist-binding domain with a weak allosteric interaction at the TARP/KGK site to slow desensitization, and a stronger interaction at a different site that slows recovery from desensitization. Together, these distinctions help explain GSG1L’s evolutionary past and how it fulfills a unique signaling role within glutamatergic synapses. TARPs and GSG1L are evolutionarily- and structurally-related AMPA receptor auxiliary subunits that differ in function through unresolved mechanisms. Here, the authors provide insight into the spatiotemporal expression, composition, and functionality of GSG1L-containing protein complexes.
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影响因子：
16.2
作者：
Dawe GB;Musgaard M;Aurousseau MRP;Nayeem N;Green T;Biggin PC;Bowie D
通讯作者：
Bowie D
影响因子：
8.8
作者：
Cais O;Herguedas B;Krol K;Cull-Candy SG;Farrant M;Greger IH
通讯作者：
Greger IH
影响因子：
16.2
作者：
Jackson AC;Nicoll RA
通讯作者：
Nicoll RA
DOI：
10.1083/jcb.141.7.1539
发表时间：
1998-06-29
期刊：
The Journal of cell biology
影响因子：
--
作者：
Furuse M;Fujita K;Hiiragi T;Fujimoto K;Tsukita S
通讯作者：
Tsukita S
影响因子：
2.9
作者：
Fukaya, M;Yamazaki, M;Watanabe, M
通讯作者：
Watanabe, M