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J Neurosci
2012 Mar 21;3212:4080-91. doi: 10.1523/JNEUROSCI.5021-11.2012.
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N-glycosylation of acid-sensing ion channel 1a regulates its trafficking and acidosis-induced spine remodeling.
Jing L
,
Chu XP
,
Jiang YQ
,
Collier DM
,
Wang B
,
Jiang Q
,
Snyder PM
,
Zha XM
.
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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. N-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 N-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.
Alvarez de la Rosa,
Distribution, subcellular localization and ontogeny of ASIC1 in the mammalian central nervous system.
2003, Pubmed
Alvarez de la Rosa,
Distribution, subcellular localization and ontogeny of ASIC1 in the mammalian central nervous system.
2003,
Pubmed
Benediktsson,
Ballistic labeling and dynamic imaging of astrocytes in organotypic hippocampal slice cultures.
2005,
Pubmed
Bhatt,
Dendritic spine dynamics.
2009,
Pubmed
Bloodgood,
Neuronal activity regulates diffusion across the neck of dendritic spines.
2005,
Pubmed
Bloodgood,
Ca(2+) signaling in dendritic spines.
2007,
Pubmed
Cai,
The role of N-glycosylation in the stability, trafficking and GABA-uptake of GABA-transporter 1. Terminal N-glycans facilitate efficient GABA-uptake activity of the GABA transporter.
2005,
Pubmed
Canessa,
Membrane topology of the epithelial sodium channel in intact cells.
1994,
Pubmed
,
Xenbase
Chen,
Automated and quantitative image analysis of ischemic dendritic blebbing using in vivo 2-photon microscopy data.
2011,
Pubmed
Cho,
Presynaptic release probability is increased in hippocampal neurons from ASIC1 knockout mice.
2008,
Pubmed
Chu,
ASIC1a-specific modulation of acid-sensing ion channels in mouse cortical neurons by redox reagents.
2006,
Pubmed
Chu,
Subunit-dependent high-affinity zinc inhibition of acid-sensing ion channels.
2004,
Pubmed
Collier,
Extracellular chloride regulates the epithelial sodium channel.
2009,
Pubmed
,
Xenbase
Collin,
Dendritic spine density and LTP induction in cultured hippocampal slices.
1997,
Pubmed
De Simoni,
Development of rat CA1 neurones in acute versus organotypic slices: role of experience in synaptic morphology and activity.
2003,
Pubmed
Duan,
Extracellular spermine exacerbates ischemic neuronal injury through sensitization of ASIC1a channels to extracellular acidosis.
2011,
Pubmed
Friese,
Acid-sensing ion channel-1 contributes to axonal degeneration in autoimmune inflammation of the central nervous system.
2007,
Pubmed
Gao,
Coupling between NMDA receptor and acid-sensing ion channel contributes to ischemic neuronal death.
2005,
Pubmed
Gonzales,
Pore architecture and ion sites in acid-sensing ion channels and P2X receptors.
2009,
Pubmed
Hebert,
The glycan code of the endoplasmic reticulum: asparagine-linked carbohydrates as protein maturation and quality-control tags.
2005,
Pubmed
Helenius,
Roles of N-linked glycans in the endoplasmic reticulum.
2004,
Pubmed
Immke,
Lactate enhances the acid-sensing Na+ channel on ischemia-sensing neurons.
2001,
Pubmed
Jasti,
Structure of acid-sensing ion channel 1 at 1.9 A resolution and low pH.
2007,
Pubmed
Jiang,
Characterization of acid-sensing ion channels in medium spiny neurons of mouse striatum.
2009,
Pubmed
Jiang,
Cysteine 149 in the extracellular finger domain of acid-sensing ion channel 1b subunit is critical for zinc-mediated inhibition.
2011,
Pubmed
Jiang,
Inhibitory regulation of acid-sensing ion channel 3 by zinc.
2010,
Pubmed
Jing,
The interaction between the first transmembrane domain and the thumb of ASIC1a is critical for its N-glycosylation and trafficking.
2011,
Pubmed
Kadurin,
Differential effects of N-glycans on surface expression suggest structural differences between the acid-sensing ion channel (ASIC) 1a and ASIC1b.
2008,
Pubmed
,
Xenbase
Kasai,
Structural dynamics of dendritic spines in memory and cognition.
2010,
Pubmed
Koch,
The function of dendritic spines: devices subserving biochemical rather than electrical compartmentalization.
1993,
Pubmed
Li,
N-Glycosylation of the human kappa opioid receptor enhances its stability but slows its trafficking along the biosynthesis pathway.
2007,
Pubmed
Majewska,
Mechanisms of calcium decay kinetics in hippocampal spines: role of spine calcium pumps and calcium diffusion through the spine neck in biochemical compartmentalization.
2000,
Pubmed
Noël,
Current perspectives on acid-sensing ion channels: new advances and therapeutic implications.
2010,
Pubmed
Noguchi,
Spine-neck geometry determines NMDA receptor-dependent Ca2+ signaling in dendrites.
2005,
Pubmed
Oliva,
Distally directed dendrotoxicity induced by kainic Acid in hippocampal interneurons of green fluorescent protein-expressing transgenic mice.
2002,
Pubmed
Prescher,
Chemical technologies for probing glycans.
2006,
Pubmed
Quirk,
Three putative N-glycosylation sites within the murine 5-HT3A receptor sequence affect plasma membrane targeting, ligand binding, and calcium influx in heterologous mammalian cells.
2004,
Pubmed
Rotin,
Trafficking and cell surface stability of ENaC.
2001,
Pubmed
Schlote,
Reversible apical swelling of dendrites in the cerebral cortex of cats during respiratory acidosis.
1975,
Pubmed
Sherwood,
Endogenous arginine-phenylalanine-amide-related peptides alter steady-state desensitization of ASIC1a.
2008,
Pubmed
,
Xenbase
Sherwood,
Dynorphin opioid peptides enhance acid-sensing ion channel 1a activity and acidosis-induced neuronal death.
2009,
Pubmed
,
Xenbase
Siesjö,
Lactic acidosis in the brain: occurrence, triggering mechanisms and pathophysiological importance.
1982,
Pubmed
Sluka,
Acid-sensing ion channels: A new target for pain and CNS diseases.
2009,
Pubmed
Vacca,
N-Glycans mutations rule oligomeric assembly and functional expression of P2X3 receptor for extracellular ATP.
2011,
Pubmed
Vukicevic,
Modulatory effects of acid-sensing ion channels on action potential generation in hippocampal neurons.
2004,
Pubmed
Waldmann,
A proton-gated cation channel involved in acid-sensing.
1997,
Pubmed
,
Xenbase
Wemmie,
The acid-activated ion channel ASIC contributes to synaptic plasticity, learning, and memory.
2002,
Pubmed
Wemmie,
Acid-sensing ion channel 1 is localized in brain regions with high synaptic density and contributes to fear conditioning.
2003,
Pubmed
Xiong,
Neuroprotection in ischemia: blocking calcium-permeable acid-sensing ion channels.
2004,
Pubmed
Yermolaieva,
Extracellular acidosis increases neuronal cell calcium by activating acid-sensing ion channel 1a.
2004,
Pubmed
Zha,
Acid-sensing ion channel 1a is a postsynaptic proton receptor that affects the density of dendritic spines.
2006,
Pubmed
Zha,
Regulation of hippocampal synapse remodeling by epileptiform activity.
2005,
Pubmed
Zha,
Oxidant regulated inter-subunit disulfide bond formation between ASIC1a subunits.
2009,
Pubmed
,
Xenbase
Zha,
ASIC2 subunits target acid-sensing ion channels to the synapse via an association with PSD-95.
2009,
Pubmed
Ziemann,
Seizure termination by acidosis depends on ASIC1a.
2008,
Pubmed
