Nuclear translocation of CAM-associated protein activates transcription for long-term facilitation in Aplysia.
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.
Lee
Seung-Hee
SH
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.
Lim
Chae-Seok
CS
Park
Hyungju
H
Lee
Jin-A
JA
Han
Jin-Hee
JH
Kim
Hyoung
H
Cheang
Ye-Hwang
YH
Lee
Sue-Hyun
SH
Lee
Yong-Seok
YS
Ko
Hyoung-Gon
HG
Jang
Dong-Hyuk
DH
Kim
Hyongkyu
H
Miniaci
Maria C
MC
Bartsch
Dusan
D
Kim
Eunjoon
E
Bailey
Craig H
CH
Kandel
Eric R
ER
Kaang
Bong-Kiun
BK
D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000818:Animals; D001048:Aplysia / Q000166:cytology / Q000378:metabolism*; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004742:Enhancer Elements, Genetic / Q000502:physiology; D006801:Humans; D017774:Long-Term Potentiation / Q000502:physiology*; D009420:Nervous System / Q000166:cytology / Q000378:metabolism*; D009475:Neurons, Afferent / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology; D015533:Transcriptional Activation / Q000502:physiology
D015816:Cell Adhesion Molecules, Neuronal; D017362:Cyclic AMP Response Element-Binding Protein; D012701:Serotonin; D017868:Cyclic AMP-Dependent Protein Kinases