Lee Seung-Hee, Lim Chae-Seok, Park Hyungju, Lee Jin-A, Han Jin-Hee, Kim Hyoung, Cheang Ye-Hwang, Lee Sue-Hyun, Lee Yong-Seok, Ko Hyoung-Gon, Jang Dong-Hyuk, Kim Hyongkyu, Miniaci Maria C, Bartsch Dusan, Kim Eunjoon, Bailey Craig H, Kandel Eric R, Kaang Bong-Kiun
Department of Biological Sciences, Institute of Molecular Biology and Genetics, RIO, College of Natural Sciences, Seoul National University, San 56-1 Silim-dong Gwanak-gu, Seoul 151-747, Korea.
Cell. 2007 May 18;129(4):801-12. doi: 10.1016/j.cell.2007.03.041.
Repeated pulses of serotonin (5-HT) induce long-term facilitation (LTF) of the synapses between sensory and motor neurons of the gill-withdrawal reflex in Aplysia. To explore how apCAM downregulation at the plasma membrane and CREB-mediated transcription in the nucleus, both of which are required for the formation of LTF, might relate to each other, we cloned an apCAM-associated protein (CAMAP) by yeast two-hybrid screening. We found that 5-HT signaling at the synapse activates PKA which in turn phosphorylates CAMAP to induce the dissociation of CAMAP from apCAM and the subsequent translocation of CAMAP into the nucleus of sensory neurons. In the nucleus, CAMAP acts as a transcriptional coactivator for CREB1 and is essential for the activation of ApC/EBP required for the initiation of LTF. Combined, our data suggest that CAMAP is a retrograde signaling component that translocates from activated synapses to the nucleus during synapse-specific LTF.
重复给予血清素（5-羟色胺，5-HT）可诱导海兔鳃缩反射中感觉神经元与运动神经元之间突触的长时程易化（LTF）。为了探究质膜上apCAM的下调与细胞核中CREB介导的转录（二者均为LTF形成所必需）之间可能存在的相互关系，我们通过酵母双杂交筛选克隆出一种apCAM相关蛋白（CAMAP）。我们发现，突触处的5-HT信号激活蛋白激酶A（PKA），PKA继而使CAMAP磷酸化，促使CAMAP与apCAM解离，随后CAMAP转位进入感觉神经元的细胞核。在细胞核中，CAMAP作为CREB1的转录共激活因子，对于启动LTF所需的ApC/EBP的激活至关重要。综合来看，我们的数据表明，CAMAP是一种逆行信号成分，在突触特异性LTF过程中从激活的突触转位至细胞核。
