TARP modulation of synaptic AMPA receptor trafficking and gating depends on multiple intracellular domains
TARP modulation of synaptic AMPA receptor trafficking and gating depends on multiple intracellular domains
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DOI：
10.1073/pnas.0905570106
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发表时间：
2009-07-07
影响因子：
11.1
通讯作者：
Nicoll, Roger A.
中科院分区：
文献类型：
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作者：
Milstein, Aaron D.;Nicoll, Roger A.
先前的工作已经建立了stargazin和其相关的跨膜AMPA受体调节蛋白家族（TARPs）作为AMPA受体（AMPAR）的辅助亚基，其通过细胞内PDZ结合基序将AMPAR靶向突触和通过细胞外结构域调节其门控来控制突触强度。然而，尽管具有相同的PDZ结合基序，但TARP γ-2和γ-8差异调节AMPAR的突触靶向。在这里，我们调查的结构要素，有助于这种功能的差异TARP亚型通过使用域移植和截断。我们确定了一个组件的突触AMPAR贩运是独立的TARP C-末端PDZ结合基序，我们建立以前未表征的作用TARP细胞内的N端，环，和C端在调制的贩运和门控的突触AMPAR。
Previous work has established stargazin and its related family of transmembrane AMPA receptor regulatory proteins (TARPs) as auxiliary subunits of AMPA receptors (AMPARs) that control synaptic strength both by targeting AMPARs to synapses through an intracellular PDZ-binding motif and by modulating their gating through an extracellular domain. However, TARPs gamma-2 and gamma-8 differentially regulate the synaptic targeting of AMPARs, despite having identical PDZ-binding motifs. Here, we investigate the structural elements that contribute to this functional difference between TARP subtypes by using domain transplantation and truncation. We identify a component of synaptic AMPAR trafficking that is independent of the TARP C-terminal PDZ-binding motif, and we establish previously uncharacterized roles for the TARP intracellular N terminus, loop, and C terminus in modulating both the trafficking and gating of synaptic AMPARs.