Journal article
Deletion of synapsins I and II genes alters the size of vesicular pools and rabphilin phosphorylation
Brain research, Vol.1107(1), pp.42-51
2006
DOI: 10.1016/j.brainres.2006.05.092
PMID: 16844103
Abstract
Previous studies established that genetic deletion of synapsins, synaptic vesicle-associated phosphoproteins that regulate neurotransmitter release, decreases the number of synaptic vesicles in nerve terminals. To investigate whether these changes affect the release properties of the remaining synaptic vesicles, we used a radioactive labeling technique to measure release independently of the total number of synaptic vesicles.
3H-glutamate and
14C-γ-amino-butyric-acid (GABA) release from isolated nerve terminals prepared from the neocortex of synapsins I and II double knock-out mice (DKO) was assayed and compared to wild-type preparations. Hyperosmotic shock-evoked
3H-glutamate was reduced by 20 ± 3% from DKO nerve terminals and potassium depolarization-evoked glutamate release was also decreased by 28 ± 2%. Surprisingly, sucrose or potassium depolarization-evoked release of
14C-GABA was increased by 32 ± 4% and 29 ± 5%, respectively. The basal efflux of both
3H-glutamate and
14C-GABA increased by 17 ± 2% and 12 ± 2% from DKO nerve terminals. As lack of synapsins I and II, major phosphoproteins of synaptic vesicles, may lead to deregulation of phosphorylation events, we compared phosphorylation state of another synaptic vesicle protein, rabphilin. In DKO nerve terminals, membrane-associated rabphilin level was reduced by ∼0.28-fold, its phosphorylation at
234serine was increased by ∼1.61-fold whereas cytosolic rabphilin levels showed both more dramatic reduction in abundance, ∼16.5-fold, and increase in phosphorylation, ∼4.8-fold. Collectively, these data suggest that deletion of major synapsin isoforms leads to (1) deregulation of basal neurotransmission causing “leaky” basal release, (2) changes in either the size or mobilization of releasable or reserve pools, and (3) a decrease in rabphilin abundance accompanied by an increase in basal phosphorylation of the remaining rabphilin.
Details
- Title: Subtitle
- Deletion of synapsins I and II genes alters the size of vesicular pools and rabphilin phosphorylation
- Creators
- György LonartFatma Simsek-Duran
- Resource Type
- Journal article
- Publication Details
- Brain research, Vol.1107(1), pp.42-51
- Publisher
- Elsevier B.V
- DOI
- 10.1016/j.brainres.2006.05.092
- PMID
- 16844103
- ISSN
- 0006-8993
- eISSN
- 1872-6240
- Language
- English
- Date published
- 2006
- Academic Unit
- Psychiatry
- Record Identifier
- 9984003974702771
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