Department of Biology, Center for Cell and Genome Science, University of Utah, Salt Lake City, UT 84112, USA.
Department of Biology, Center for Cell and Genome Science, University of Utah, Salt Lake City, UT 84112, USA.
Neuron. 2013 Dec 18;80(6):1421-37. doi: 10.1016/j.neuron.2013.10.050.
A primary determinant of the strength of neurotransmission is the number of AMPA-type glutamate receptors (AMPARs) at synapses. However, we still lack a mechanistic understanding of how the number of synaptic AMPARs is regulated. Here, we show that UNC-116, the C. elegans homolog of vertebrate kinesin-1 heavy chain (KIF5), modifies synaptic strength by mediating the rapid delivery, removal, and redistribution of synaptic AMPARs. Furthermore, by studying the real-time transport of C. elegans AMPAR subunits in vivo, we demonstrate that although homomeric GLR-1 AMPARs can diffuse to and accumulate at synapses in unc-116 mutants, glutamate-gated currents are diminished because heteromeric GLR-1/GLR-2 receptors do not reach synapses in the absence of UNC-116/KIF5-mediated transport. Our data support a model in which ongoing motor-driven delivery and removal of AMPARs controls not only the number but also the composition of synaptic AMPARs, and thus the strength of synaptic transmission.
神经递质传递强度的一个主要决定因素是突触处 AMPA 型谷氨酸受体 (AMPARs) 的数量。然而，我们仍然缺乏对突触 AMPAR 数量如何调节的机制理解。在这里，我们表明 UNC-116（秀丽隐杆线虫脊椎动物驱动蛋白-1 重链 (KIF5) 的同源物）通过介导突触 AMPAR 的快速传递、去除和再分布来调节突触强度。此外，通过研究秀丽隐杆线虫 AMPAR 亚基在体内的实时运输，我们证明尽管同型 GLR-1 AMPAR 可以扩散到 unc-116 突变体中的突触并积累，但由于没有 UNC-116/KIF5 介导的运输，异源 GLR-1/GLR-2 受体无法到达突触，因此谷氨酸门控电流减少。我们的数据支持这样一种模型，即持续的马达驱动的 AMPAR 传递和去除不仅控制着突触 AMPAR 的数量，而且控制着其组成，从而控制着突触传递的强度。
