Cooperative regulation of neurotransmitter release by Rab3a and synapsin II.
Mol Cell Neurosci
; 44(2): 190-200, 2010 Jun.
Article
in En
| MEDLINE
| ID: mdl-20338242
ABSTRACT
To understand how the presynaptic proteins synapsin and Rab3a may interact in the regulation of the synaptic vesicle cycle and the release process, we derived a double knockout (DKO) mouse lacking both synapsin II and Rab3a. We found that Rab3a deletion rescued epileptic-like seizures typical for synapsin II gene deleted animals (Syn II(-)). Furthermore, action potential evoked release was drastically reduced in DKO synapses, although spontaneous release remained normal. At low Ca2+ conditions, quantal content was equally reduced in Rab3a(-) and DKO synapses, but as Ca2+ concentration increased, the increase in quantal content was more prominent in Rab3a(-). Electron microscopy analysis revealed that DKO synapses have a combined phenotype, with docked vesicles being reduced similar to Rab3a(-), and intraterminal vesicles being depleted similar to Syn II(-). Consistently, both Syn II(-) and DKO terminals had increased synaptic depression and incomplete recovery. Taken together, our results suggest that synapsin II and Rab3a have separate roles in maintaining the total store of synaptic vesicles and cooperate in promoting the latest steps of neuronal secretion.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Synaptic Vesicles
/
Synapsins
/
Presynaptic Terminals
/
Synaptic Transmission
/
Neurotransmitter Agents
/
Rab3A GTP-Binding Protein
Limits:
Animals
Language:
En
Journal:
Mol Cell Neurosci
Journal subject:
BIOLOGIA MOLECULAR
/
NEUROLOGIA
Year:
2010
Document type:
Article
Affiliation country:
Estados Unidos