Department of Biology, University of Utah, Salt Lake City, UT 84112-0840, USA.
Neuron. 2012 Sep 6;75(5):838-50. doi: 10.1016/j.neuron.2012.06.038.
The neurotransmitter glutamate mediates excitatory synaptic transmission by gating ionotropic glutamate receptors (iGluRs). AMPA receptors (AMPARs), a subtype of iGluR, are strongly implicated in synaptic plasticity, learning, and memory. We previously discovered two classes of AMPAR auxiliary proteins in C. elegans that modify receptor kinetics and thus change synaptic transmission. Here, we have identified another auxiliary protein, SOL-2, a CUB-domain protein that associates with both the related auxiliary subunit SOL-1 and with the GLR-1 AMPAR. In sol-2 mutants, behaviors dependent on glutamatergic transmission are disrupted, GLR-1-mediated currents are diminished, and GLR-1 desensitization and pharmacology are modified. Remarkably, a secreted variant of SOL-1 delivered in trans can rescue sol-1 mutants, and this rescue depends on in cis expression of SOL-2. Finally, we demonstrate that SOL-1 and SOL-2 have an ongoing role in the adult nervous system to control AMPAR-mediated currents.
神经递质谷氨酸通过门控离子型谷氨酸受体（iGluR）介导兴奋性突触传递。AMPA 受体（AMPAR）是 iGluR 的一种亚型，强烈参与突触可塑性、学习和记忆。我们之前在秀丽隐杆线虫中发现了两类 AMPAR 辅助蛋白，它们可以改变受体动力学，从而改变突触传递。在这里，我们鉴定出了另一种辅助蛋白 SOL-2，它是一种 CUB 结构域蛋白，与相关的辅助亚基 SOL-1 和 GLR-1 AMPAR 都有关联。在 sol-2 突变体中，依赖于谷氨酸能传递的行为被破坏，GLR-1 介导的电流减少，GLR-1 脱敏和药理学性质被改变。值得注意的是，转位表达的 SOL-1 的分泌变体可以拯救 sol-1 突变体，而这种拯救依赖于 SOL-2 的顺式表达。最后，我们证明 SOL-1 和 SOL-2 在成年神经系统中具有持续的作用，以控制 AMPAR 介导的电流。
