Chen L, Chetkovich D M, Petralia R S, Sweeney N T, Kawasaki Y, Wenthold R J, Bredt D S, Nicoll R A
Department of Cellular and Molecular Pharmacology, University of California, San Francisco 94143, USA.
Nature. 2000;408(6815):936-43. doi: 10.1038/35050030.
Stargazer, an ataxic and epileptic mutant mouse, lacks functional AMPA (alpha-amino-3-hydroxyl-5-methyl-4-isoxazolepropionate) receptors on cerebellar granule cells. Stargazin, the mutated protein, interacts with both AMPA receptor subunits and synaptic PDZ proteins, such as PSD-95. The interaction of stargazin with AMPA receptor subunits is essential for delivering functional receptors to the surface membrane of granule cells, whereas its binding with PSD-95 and related PDZ proteins through a carboxy-terminal PDZ-binding domain is required for targeting the AMPA receptor to synapses. Expression of a mutant stargazin lacking the PDZ-binding domain in hippocampal pyramidal cells disrupts synaptic AMPA receptors, indicating that stargazin-like mechanisms for targeting AMPA receptors may be widespread in the central nervous system.
“凝视者”是一种患有共济失调和癫痫的突变小鼠，其小脑颗粒细胞上缺乏功能性的AMPA（α-氨基-3-羟基-5-甲基-4-异恶唑丙酸）受体。突变蛋白stargazin与AMPA受体亚基以及突触PDZ蛋白（如PSD-95）相互作用。stargazin与AMPA受体亚基的相互作用对于将功能性受体递送至颗粒细胞的表面膜至关重要，而其通过羧基末端PDZ结合结构域与PSD-95及相关PDZ蛋白的结合则是将AMPA受体靶向突触所必需的。在海马锥体细胞中表达缺乏PDZ结合结构域的突变stargazin会破坏突触AMPA受体，这表明靶向AMPA受体的类似stargazin的机制可能在中枢神经系统中广泛存在。
