Department of Clinical Neurobiology, University of Heidelberg, 6910 Heidelberg, Germany.
Science. 2010 Mar 19;327(5972):1518-22. doi: 10.1126/science.1184178. Epub 2010 Feb 25.
CKAMP44, identified here by a proteomic approach, is a brain-specific type I transmembrane protein that associates with AMPA receptors in synaptic spines. CKAMP44 expressed in Xenopus oocytes reduced GluA1- and A2-mediated steady-state currents, but did not affect kainate- or N-methyl-D-aspartate (NMDA) receptor-mediated currents. Mouse hippocampal CA1 pyramidal neurons expressed CKAMP44 at low abundance, and overexpression of CKAMP44 led to stronger and faster AMPA receptor desensitization, slower recovery from desensitization, and a reduction in the paired-pulse ratio of AMPA currents. By contrast, dentate gyrus granule cells exhibited strong CKAMP44 expression, and CKAMP44 knockout increased the paired-pulse ratio of AMPA currents in lateral and medial perforant path-granule cell synapses. CKAMP44 thus modulates short-term plasticity at specific excitatory synapses.
在这里通过蛋白质组学方法鉴定出的 CKAMP44 是一种脑特异性的 I 型跨膜蛋白,它在突触棘突中与 AMPA 受体结合。在非洲爪蟾卵母细胞中表达的 CKAMP44 减少了 GluA1 和 A2 介导的稳态电流,但不影响海人藻酸或 N-甲基-D-天冬氨酸(NMDA)受体介导的电流。小鼠海马 CA1 锥体神经元以低丰度表达 CKAMP44,过表达 CKAMP44 导致 AMPA 受体脱敏更强更快,脱敏后恢复更慢,以及 AMPA 电流的成对脉冲比降低。相比之下,齿状回颗粒细胞表现出强烈的 CKAMP44 表达,而 CKAMP44 敲除增加了外侧和内侧穿通纤维-颗粒细胞突触中 AMPA 电流的成对脉冲比。因此,CKAMP44 调节特定兴奋性突触的短期可塑性。