Shepherd Jason D, Huganir Richard L
The Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Annu Rev Cell Dev Biol. 2007;23:613-43. doi: 10.1146/annurev.cellbio.23.090506.123516.
The cellular processes that govern neuronal function are highly complex, with many basic cell biological pathways uniquely adapted to perform the elaborate information processing achieved by the brain. This is particularly evident in the trafficking and regulation of membrane proteins to and from synapses, which can be a long distance away from the cell body and number in the thousands. The regulation of neurotransmitter receptors, such as the AMPA-type glutamate receptors (AMPARs), the major excitatory neurotransmitter receptors in the brain, is a crucial mechanism for the modulation of synaptic transmission. The levels of AMPARs at synapses are very dynamic, and it is these plastic changes in synaptic function that are thought to underlie information storage in the brain. Thus, understanding the cellular machinery that controls AMPAR trafficking will be critical for understanding the cellular basis of behavior as well as many neurological diseases. Here we describe the life cycle of AMPARs, from their biogenesis, through their journey to the synapse, and ultimately through their demise, and discuss how the modulation of this process is essential for brain function.
支配神经元功能的细胞过程极其复杂,许多基本的细胞生物学途径都经过独特的适应性调整,以执行大脑所实现的精细信息处理。这在膜蛋白往返突触的运输和调节过程中尤为明显,突触可能距离细胞体很远,数量可达数千个。神经递质受体的调节,如大脑中主要的兴奋性神经递质受体AMPA型谷氨酸受体(AMPARs),是调节突触传递的关键机制。突触处AMPARs的水平非常动态,正是这些突触功能的可塑性变化被认为是大脑信息存储的基础。因此,了解控制AMPAR运输的细胞机制对于理解行为的细胞基础以及许多神经系统疾病至关重要。在这里,我们描述了AMPARs的生命周期,从它们的生物发生,到它们前往突触的旅程,最终到它们的消亡,并讨论了对这一过程的调节如何对大脑功能至关重要。