Role of Aplysia cell adhesion molecules during 5-HT-induced long-term functional and structural changes.
We previously reported that five repeated pulses of 5-HT lead to down-regulation of the TM-apCAM isoform at the surface of Aplysia sensory neurons (SNs). We here examined whether apCAM down-regulation is required for 5-HT-induced long-term facilitation. We also analyzed the role of the cytoplasmic and extracellular domains by overexpressing various apCAM mutants by DNA microinjection. When TM-apCAM was up-regulated in SNs by DNA microinjection, five pulses of 5-HT failed to produce either synaptic facilitation or an enhancement of synaptic growth, suggesting that down-regulation of apCAM is required for 5-HT-induced EPSP enhancement and new varicosity formation. However, disrupting the extracellular domain function of overexpressed apCAM with a specific antibody restored 5-HT-induced excitatory postsynaptic potential increase but not synaptic growth. The overexpression of the MAP Kinase mutant of TM-apCAM, which is not internalized by 5-HT, inhibited new varicosity formation, but did not inhibit excitatory postsynaptic potential increase. Deletion mutants containing only the cytoplasmic portion of apCAM blocked 5-HT-induced synaptic growth but not excitatory postsynaptic potential increase. Thus, our data suggest that TM-apCAM may act as a suppressor of both synaptic-strength enhancement in pre-existing synapses and of new synaptic varicosity formation in the nonsynaptic region, via different mechanisms.
Han
Jin-Hee
JH
National Research Laboratory of Neurobiology, Institute of Molecular Biology and Genetics, School of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul 151-742, Korea.
Lim
Chae-Seok
CS
Lee
Yong-Seok
YS
Kandel
Eric R
ER
Kaang
Bong-Kiun
BK
D000818:Animals; D001048:Aplysia / Q000235:genetics / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D004247:DNA / Q000008:administration & dosage; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D017952:Ganglia, Invertebrate / Q000166:cytology / Q000502:physiology; D017353:Gene Deletion; D005786:Gene Expression Regulation; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000502:physiology*; D008845:Microinjections; D009475:Neurons, Afferent / Q000502:physiology*; D017434:Protein Structure, Tertiary / Q000502:physiology; D012701:Serotonin / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D013329:Structure-Activity Relationship; D013569:Synapses / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology*
D015815:Cell Adhesion Molecules; D012701:Serotonin; D004247:DNA