TY - JOUR
T1 - Suppression of long-term facilitation by Rab3-effector protein interaction
AU - Han, Jin Hee
AU - Lee, Changhoon
AU - Cheang, Yehwang
AU - Kaang, Bong Kiun
N1 - Funding Information:
This work was supported by the Korea Ministry of Science and Technology under National Research Laboratory Program (M1-0104-00-0140) and BRC-Frontier Program (M103KV010012 03K2201 01210) and by the Marine and Extreme Genome Research Center Program, Ministry of Marine Affairs and Fisheries, Republic of Korea. J.-H.H., Y.C. were supported by a BK21 Research Fellowship from the Korea Ministry of Education and Human Resources Development.
PY - 2005/9/13
Y1 - 2005/9/13
N2 - 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.
AB - 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.
KW - 5-HT
KW - Aplysia
KW - apRab3
KW - Basal synaptic transmission
KW - Long-term facilitation
KW - Microinjection
UR - http://www.scopus.com/inward/record.url?scp=27744530589&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=27744530589&partnerID=8YFLogxK
U2 - 10.1016/j.molbrainres.2005.05.004
DO - 10.1016/j.molbrainres.2005.05.004
M3 - Article
C2 - 15936113
AN - SCOPUS:27744530589
SN - 0006-8993
VL - 139
SP - 13
EP - 22
JO - Brain Research
JF - Brain Research
IS - 1
ER -