Journal article
N-Glycosylation of Acid-Sensing Ion Channel 1a Regulates Its Trafficking and Acidosis-Induced Spine Remodeling
The Journal of neuroscience, Vol.32(12), pp.4080-4091
03/21/2012
DOI: 10.1523/JNEUROSCI.5021-11.2012
PMCID: PMC3322463
PMID: 22442073
Abstract
Acid-sensing ion channel-1a (ASIC1a) is a potential therapeutic target for multiple neurological diseases. We studied here ASIC1a glycosylation and trafficking, two poorly understood processes pivotal in determining the functional outcome of an ion channel. We found that most ASIC1a in the mouse brain was fully glycosylated. Inhibiting glycosylation with tunicamycin reduced ASIC1a surface trafficking, dendritic targeting, and acid-activated current density.
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-glycosylation of the two glycosylation sites, Asn393 and Asn366, has differential effects on ASIC1a biogenesis. Maturation of Asn393 increased ASIC1a surface and dendritic trafficking, pH sensitivity, and current density. In contrast, glycosylation of Asn366 was dispensable for ASIC1a function and may be a rate-limiting step in ASIC1a biogenesis. In addition, we revealed that acidosis reduced the density and length of dendritic spines in a time- and ASIC1a-dependent manner. ASIC1a N366Q, which showed increased glycosylation and dendritic targeting, potentiated acidosis-induced spine loss. Conversely, ASIC1a N393Q, which had diminished dendritic targeting and inhibited ASIC1a current dominant-negatively, had the opposite effect. These data tie
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-glycosylation of ASIC1a with its trafficking. More importantly, by revealing a site-specific effect of acidosis on dendritic spines, our findings suggest that these processes have an important role in regulating synaptic plasticity and determining long-term consequences in diseases that generate acidosis.
Details
- Title: Subtitle
- N-Glycosylation of Acid-Sensing Ion Channel 1a Regulates Its Trafficking and Acidosis-Induced Spine Remodeling
- Creators
- Lan Jing - Department of Cell Biology and Neuroscience, University of South Alabama College of Medicine, Mobile, Alabama 36688Xiang-Ping Chu - Departments of Basic Medical Science and Anesthesiology, University of Missouri-Kansas City School of Medicine, Kansas City, Missouri 64108Yu-Qing Jiang - Department of Cell Biology and Neuroscience, University of South Alabama College of Medicine, Mobile, Alabama 36688Daniel M Collier - Departments of Internal Medicine and Molecular Physiology and Biophysics, University of Iowa, Iowa City, Iowa 52242, andBin Wang - Department of Mathematics and Statistics, University of South Alabama, Mobile, Alabama 36688Qian Jiang - Departments of Basic Medical Science and Anesthesiology, University of Missouri-Kansas City School of Medicine, Kansas City, Missouri 64108Peter M Snyder - Departments of Internal Medicine and Molecular Physiology and Biophysics, University of Iowa, Iowa City, Iowa 52242, andXiang-Ming Zha - Department of Cell Biology and Neuroscience, University of South Alabama College of Medicine, Mobile, Alabama 36688
- Resource Type
- Journal article
- Publication Details
- The Journal of neuroscience, Vol.32(12), pp.4080-4091
- Publisher
- Society for Neuroscience
- DOI
- 10.1523/JNEUROSCI.5021-11.2012
- PMID
- 22442073
- PMCID
- PMC3322463
- ISSN
- 0270-6474
- eISSN
- 1529-2401
- Language
- English
- Date published
- 03/21/2012
- Academic Unit
- Molecular Physiology and Biophysics; Cardiovascular Medicine; Medicine Administration; Internal Medicine
- Record Identifier
- 9984025574502771
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