Journal article
Synaptic vesicle recycling is enhanced by torsinA that harbors the DYT1 dystonia mutation
Synapse (New York, N.Y.), Vol.66(5), pp.453-464
05/2012
DOI: 10.1002/syn.21534
PMID: 22213465
Abstract
Early-onset generalized dystonia, DYT1, is caused by a mutation in the gene encoding the evolutionarily conserved AAA+ ATPase torsinA. Synaptic abnormalities have been implicated in DYT1 dystonia, but the details of the synaptic pathophysiology are only partially understood. Here, we demonstrate a novel role for torsinA in synaptic vesicle recycling, using cultured hippocampal neurons from a knock-in mouse model of DYT1 dystonia (ΔE-torsinA) and live-cell imaging with styryl FM dyes. Neurons from heterozygous ΔE-torsinA mice released a larger fraction of the total recycling pool (TRP) during a single round of electrical stimulation than did wild-type neurons. Moreover, when the neurons were subjected to prior high activity, the time course of release was shortened. In neurons from homozygous mice, these enhanced exocytosis phenotypes were similar, but in addition the size of the TRP was reduced. Notably, when release was triggered by applying a calcium ionophore rather than electrical stimuli, neither a single nor two ΔE-torsinA alleles affected the time course of release. Thus, the site of action of ΔE-torsinA is at or upstream of the rise in calcium concentration in nerve terminals. Our results suggest that torsinA regulates synaptic vesicle recycling in central neurons. They also indicate that this regulation is influenced by neuronal activity, further supporting the idea that synaptic abnormalities contribute to the pathophysiology of DYT1 dystonia.
Details
- Title: Subtitle
- Synaptic vesicle recycling is enhanced by torsinA that harbors the DYT1 dystonia mutation
- Creators
- Yasuhiro Kakazu - Department of Molecular Physiology and Biophysics, University of Iowa Carver College of Medicine, Iowa City, Iowa, USAJin-Young KohK W David HoPedro Gonzalez-AlegreN Charles Harata
- Resource Type
- Journal article
- Publication Details
- Synapse (New York, N.Y.), Vol.66(5), pp.453-464
- Publisher
- United States
- DOI
- 10.1002/syn.21534
- PMID
- 22213465
- ISSN
- 0887-4476
- eISSN
- 1098-2396
- Grant note
- T32 GM007337 / NIGMS NIH HHS
- Language
- English
- Date published
- 05/2012
- Academic Unit
- Molecular Physiology and Biophysics; Otolaryngology
- Record Identifier
- 9984025675402771
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