Suppression of long-term facilitation by Rab3-effector protein interaction.
Long-term facilitation (LTF) in Aplysia is achieved by the modulation of presynaptic release. However, the underlying mechanism that might be related with the regulation of synaptic vesicle release remains unknown. Since Rab3, a neuronal GTP-binding protein, is known to be a key regulator of synaptic vesicle fusion, we investigated the involvement of Rab3 in LTF. To address this issue, we examined the effect of overexpression of wild type Aplysia Rab3 (apRab3) and its mutant forms on LTF. Overexpression of either apRab3 Q80L, a constitutively active apRab3 mutant, or wild type apRab3 completely inhibited LTF. This inhibitory role of apRab3 appears to be mediated by an interaction with an effector molecule(s), possibly Rim. Expression of apRab3 Q80L, V54E double mutant, which do not bind effector molecules such as Rim or Rabphilin, had no effect on LTF. Furthermore, expression of apRab3 Q80L, F18L, D19E triple mutant, which has reduced binding activity with Rim but normally binds with Rabphilin, enhanced evoked basal synaptic release, and the increase in synaptic strength occluded LTF. In conclusion, our data suggest that apRab3 may act as a negative clamp of LTF through the interaction with effector protein(s), possibly Rim.
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, San 56-1 Silim-dong Kwanak-gu, Seoul 151-742, South Korea.
Lee
Changhoon
C
Cheang
Yehwang
Y
Kaang
Bong-Kiun
BK
D000595:Amino Acid Sequence; D000818:Animals; D001048:Aplysia / Q000502:physiology; D002478:Cells, Cultured; D004594:Electrophysiology; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017774:Long-Term Potentiation / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D016415:Sequence Alignment; D009435:Synaptic Transmission / Q000502:physiology; D020692:rab3 GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
D009419:Nerve Tissue Proteins; D019204:GTP-Binding Proteins; D020692:rab3 GTP-Binding Proteins