ASIC2a-dependent increase of ASIC3 surface expression enhances the sustained component of the currents
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Acid-sensing ion channels (ASICs) are proton-gated cation channels widely expressed in the nervous system. Proton sensing by ASICs has been known to mediate pain, mechanosensation, taste transduction, learning and memory, and fear. In this study, we investigated the differential subcellular localization of ASIC2a and ASIC3 in heterologous expression systems. While ASIC2a targeted the cell surface itself, ASIC3 was mostly accumulated in the ER with partial expression in the plasma membrane. However, when ASIC3 was co-expressed with ASIC2a, its surface expression was markedly increased. By using bimolecular fluorescence complementation (BiFC) assay, we confirmed the heteromeric association between ASIC2a and ASIC3 subunits. In addition, we observed that the ASIC2a-dependent surface trafficking of ASIC3 remarkably enhanced the sustained component of the currents. Our study demonstrates that ASIC2a can increase the membrane conductance sensitivity to protons by facilitating the surface expression of ASIC3 through herteromeric assembly.
Abstract
Acid-sensing ion channels (ASICs) are proton-gated cation channels widely expressed in the nervous system. Proton sensing by ASICs has been known to mediate pain, mechanosensation, taste transduction, learning and memory, and fear. In this study, we investigated the differential subcellular localization of ASIC2a and ASIC3 in heterologous expression systems. While ASIC2a targeted the cell surface itself, ASIC3 was mostly accumulated in the ER with partial expression in the plasma membrane. However, when ASIC3 was co-expressed with ASIC2a, its surface expression was markedly increased. By using bimolecular fluorescence complementation (BiFC) assay, we confirmed the heteromeric association between ASIC2a and ASIC3 subunits. In addition, we observed that the ASIC2a-dependent surface trafficking of ASIC3 remarkably enhanced the sustained component of the currents. Our study demonstrates that ASIC2a can increase the membrane conductance sensitivity to protons by facilitating the surface expression of ASIC3 through herteromeric assembly.
참고문헌 (33)
- Price MP, "Cloning and expression of a novel human brain Na+ channel", J Biol Chem, 271, pp.7879~7882 (1996)
- Waldmann R, "A proton-gated cation channel involved in acid-sensing", Nature, 386, pp.173~177 (1997)
- Deval E, "ASIC3, a sensor of acidic and primary inflammatory pain", EMBO J, 27, pp.3047~3055 (2008)
- Ikeuchi M, "Role of ASIC3 in the primary and secondary hyperalgesia produced by joint inflammation in mice", Pain, 137, pp.662~669 (2008)
- Gupta SC, "Regulation of breast tumorigenesis through acid sensors", Oncogene (2016)
- Smith ML, "Changes in extra-and intracellular pH in the brain during and following ischemia in hyperglycemic and in moderately hypoglycemic rats", J Cereb Blood Flow Metab, 6, pp.574~583 (1986)
- Du J, "Protons are a neurotransmitter that regulates synaptic plasticity in the lateral amygdala", Proc Natl Acad Sci U S A, 111, pp.8961~8966 (2014)
- Wemmie JA, "The acid-activated ion channel ASIC contributes to synaptic plasticity, learning, and memory", Neuron, 34, pp.463~477 (2002)
- Wemmie JA, "Acid-sensing ion channel 1 is localized in brain regions with high synaptic density and contributes to fear conditioning", J Neurosci, 23, pp.5496~5502 (2003)
- Ugawa S, "Amilorideinsensitive currents of the acid-sensing ion channel-2a(ASIC2a)", ASIC2b heteromeric sour-taste receptor channel, 2003, pp.23, 3616~3622
- Chen CC, "Neurosensory mechanotransduction through acid-sensing ion channels", J Cell Mol Med, 17, pp.337~349 (2013)
- Peng Z, "ASIC3 mediates itch sensation in response to coincident stimulation by acid and nonproton ligand", Cell Rep, 13, pp.387~398 (2015)
- 권해진, "Acid-sensing ion channels (ASICs): therapeutic targets for neurological diseases and their regulation", BMB Reports, 46(6), pp.295~304 (2013), 생화학분자생물학회
- Jasti J, "Structure of acid-sensing ion channel 1 at 1. 9 A resolution and low pH", Nature, 449, pp.316~323 (2007)
- Ma D, "ER transport signals and trafficking of potassium channels and receptors", Curr Opin Neurobiol, 12, pp.287~292 (2002)
- Michelsen K, "Hide and run. Arginine-based endoplasmic-reticulum-sorting motifs in the assembly of heteromultimeric membrane proteins", EMBO Rep, 6, pp.717~722 (2005)
- Ma D, "Role of ER export signals in controlling surface potassium channel numbers", Science, 291, pp.316~319 (2001)
- Chai S, "A kinase-anchoring protein 150 and calcineurin are involved in regulation of acid-sensing ion channels ASIC1a and ASIC2a", J Biol Chem, 282, pp.22668~22677 (2007)
- Chai S, "Activation of acid-sensing ion channel 1a(ASIC1a)by surface trafficking", J Biol Chem, 285, pp.13002~13011 (2010)
- Hruska-Hageman AM, "PSD-95 and Lin-7b interact with acid-sensing ion channel-3 and have opposite effects on H+-gated current", J Biol Chem, 279, pp.46962~46968 (2004)
- Deval E, "Regulation of sensory neuron-specific acid-sensing ion channel 3 by the adaptor protein Na+", H+ exchanger regulatory factor-1, 2006, pp.281, 1796~1807
- Harding AM, "ASIC2 subunits facilitate expression at the cell surface and confer regulation by PSD-95", PLoS One, 9, pp.e93797~ (2014)
- Jiang N, "Region specific contribution of ASIC2 to acidosis-and ischemia-induced neuronal injury", J Cereb Blood Flow Metab (2016)
- Shyu YJ, "Identification of new fluorescent protein fragments for bimolecular fluorescence complementation analysis under physiological conditions", Biotechniques, 40, pp.61~66 (2006)
- Hattori T, "ASIC2a and ASIC3 heteromultimerize to form pH-sensitive channels in mouse cardiac dorsal root ganglia neurons", Circ Res, 105, pp.279~286 (2009)
- Hesselager M, "pH Dependency and desensitization kinetics of heterologously expressed combinations of acid-sensing ion channel subunits", J Biol Chem, 279, pp.11006~11015 (2004)
- Babinski K, "Mammalian ASIC2a and ASIC3 subunits co-assemble into heteromeric proton-gated channels sensitive to Gd3+", J Biol Chem, 275, pp.28519~28525 (2000)
- Fu H, "Acid-sensing ion channels in trigeminal ganglion neurons innervating the orofacial region contribute to orofacial inflammatory pain", Clin Exp Pharmacol Physiol, 43, pp.193~202 (2016)
- Wu J, "ASIC subunit ratio and differential surface trafficking in the brain", Mol Brain, 9, pp.4~ (2016)
- Kweon HJ, "Differential regulation of proton-sensitive ion channels by phospholipids: a comparative study between ASICs and TRPV1", PLoS One, 10, pp.e0122014~ (2015)
- Murase K, "Excitatory and inhibitory amino acids and peptide-induced responses in acutely isolated rat spinal dorsal horn neurons", Neurosci Lett, 103, pp.56~63 (1989)
- 이형선, "Anti-oxidizing effect of the dichloromethane and hexane fractions from Orostachys japonicus in LPS-stimulated RAW 264.7 cells via upregulation of Nrf2 expression and activation of MAPK signaling pathway", BMB Reports, 47(2), pp.98~103 (2014), 생화학분자생물학회
- 고아름, "Mannitol induces selective astroglial death in the CA1 region of the rat hippocampus following status epilepticus", BMB Reports, 48(9), pp.507~512 (2015), 생화학분자생물학회
