Demonstration of a Direct Interaction Between Sigma-1 Receptors and Acid-sensing Ion Channels

Overview

Journal Biophys J

Publisher Cell Press

Specialty Biophysics

Date 2010 Apr 8

PMID 20371317

Citations 41

Authors

Stewart M Carnally

Molly Johannessen

Robert M Henderson

Meyer B Jackson

J Michael Edwardson

Affiliations

Soon will be listed here.

Abstract

The sigma-1 receptor is a widely expressed protein that interacts with a variety of ion channels, including the acid-sensing ion channel (ASIC) 1a. Here we used atomic force microscopy to determine the architecture of the ASIC1a/sigma-1 receptor complex. When isolated His(8)-tagged ASIC1a was imaged in complex with anti-His(6) antibodies, the angle between pairs of bound antibodies was 135 degrees , consistent with the known trimeric structure of the channel. When ASIC1a was coexpressed with FLAG/His(6)-tagged sigma-1 receptor, ASIC1a became decorated with small particles, and pairs of these particles bound at an angle of 131 degrees . When these complexes were incubated with anti-FLAG antibodies, pairs of antibodies bound at an angle of 134 degrees , confirming that the small particles were sigma-1 receptors. Of interest, we found that the sigma-1 receptor ligand haloperidol caused an approximately 50% reduction in ASIC1a/sigma-receptor binding, suggesting a way in which sigma-1 ligands might modulate channel properties. For the first time, to our knowledge, we have resolved the structure of a complex between the sigma-1 receptor and a target ion channel, and demonstrated that the stoichiometry of the interaction is 1 sigma-1 receptor/1 ASIC1a subunit.

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References

Carnally S, Dev H, Stewart A, Barrera N, van Bemmelen M, Schild L . Direct visualization of the trimeric structure of the ASIC1a channel, using AFM imaging. Biochem Biophys Res Commun. 2008; 372(4):752-5. DOI: 10.1016/j.bbrc.2008.05.100. View

Martin W, EADES C, Thompson J, Huppler R, Gilbert P . The effects of morphine- and nalorphine- like drugs in the nondependent and morphine-dependent chronic spinal dog. J Pharmacol Exp Ther. 1976; 197(3):517-32. View

Jasti J, Furukawa H, Gonzales E, Gouaux E . Structure of acid-sensing ion channel 1 at 1.9 A resolution and low pH. Nature. 2007; 449(7160):316-23. DOI: 10.1038/nature06163. View

Meltzer R, Kapoor N, Qadri Y, Anderson S, Fuller C, Benos D . Heteromeric assembly of acid-sensitive ion channel and epithelial sodium channel subunits. J Biol Chem. 2007; 282(35):25548-59. DOI: 10.1074/jbc.M703825200. View

Schuck S, Honsho M, Ekroos K, Shevchenko A, Simons K . Resistance of cell membranes to different detergents. Proc Natl Acad Sci U S A. 2003; 100(10):5795-800. PMC: 156280. DOI: 10.1073/pnas.0631579100. View

Lupardus P, Wilke R, Aydar E, Palmer C, Chen Y, Ruoho A . Membrane-delimited coupling between sigma receptors and K+ channels in rat neurohypophysial terminals requires neither G-protein nor ATP. J Physiol. 2000; 526 Pt 3:527-39. PMC: 2270035. DOI: 10.1111/j.1469-7793.2000.00527.x. View

Monnet F . Sigma-1 receptor as regulator of neuronal intracellular Ca2+: clinical and therapeutic relevance. Biol Cell. 2005; 97(12):873-83. DOI: 10.1042/BC20040149. View

Barrera N, Ge H, Henderson R, Fitzgerald W, Edwardson J . Automated analysis of the architecture of receptors, imaged by atomic force microscopy. Micron. 2007; 39(2):101-10. DOI: 10.1016/j.micron.2006.12.006. View

Aydar E, Palmer C, Klyachko V, Jackson M . The sigma receptor as a ligand-regulated auxiliary potassium channel subunit. Neuron. 2002; 34(3):399-410. DOI: 10.1016/s0896-6273(02)00677-3. View

10.

Pal A, Hajipour A, Fontanilla D, Ramachandran S, Chu U, Mavlyutov T . Identification of regions of the sigma-1 receptor ligand binding site using a novel photoprobe. Mol Pharmacol. 2007; 72(4):921-33. DOI: 10.1124/mol.107.038307. View

11.

Herrera Y, Katnik C, Rodriguez J, Hall A, Willing A, Pennypacker K . sigma-1 receptor modulation of acid-sensing ion channel a (ASIC1a) and ASIC1a-induced Ca2+ influx in rat cortical neurons. J Pharmacol Exp Ther. 2008; 327(2):491-502. DOI: 10.1124/jpet.108.143974. View

12.

Wong W, Schlichter L . Differential recruitment of Kv1.4 and Kv4.2 to lipid rafts by PSD-95. J Biol Chem. 2003; 279(1):444-52. DOI: 10.1074/jbc.M304675200. View

13.

Hanner M, Moebius F, Flandorfer A, Knaus H, Striessnig J, KEMPNER E . Purification, molecular cloning, and expression of the mammalian sigma1-binding site. Proc Natl Acad Sci U S A. 1996; 93(15):8072-7. PMC: 38877. DOI: 10.1073/pnas.93.15.8072. View

14.

Ishiguro H, Ohtsuki T, Toru M, Itokawa M, Aoki J, Shibuya H . Association between polymorphisms in the type 1 sigma receptor gene and schizophrenia. Neurosci Lett. 1998; 257(1):45-8. DOI: 10.1016/s0304-3940(98)00797-6. View

15.

Martens J, Sakamoto N, Sullivan S, Grobaski T, Tamkun M . Isoform-specific localization of voltage-gated K+ channels to distinct lipid raft populations. Targeting of Kv1.5 to caveolae. J Biol Chem. 2000; 276(11):8409-14. DOI: 10.1074/jbc.M009948200. View

16.

Neaves K, Cooper L, White J, Carnally S, Dryden D, Edwardson J . Atomic force microscopy of the EcoKI Type I DNA restriction enzyme bound to DNA shows enzyme dimerization and DNA looping. Nucleic Acids Res. 2009; 37(6):2053-63. PMC: 2665228. DOI: 10.1093/nar/gkp042. View

17.

Yermolaieva O, Leonard A, Schnizler M, Abboud F, Welsh M . Extracellular acidosis increases neuronal cell calcium by activating acid-sensing ion channel 1a. Proc Natl Acad Sci U S A. 2004; 101(17):6752-7. PMC: 404117. DOI: 10.1073/pnas.0308636100. View

18.

Barrera N, Betts J, You H, Henderson R, Martin I, Dunn S . Atomic force microscopy reveals the stoichiometry and subunit arrangement of the alpha4beta3delta GABA(A) receptor. Mol Pharmacol. 2007; 73(3):960-7. DOI: 10.1124/mol.107.042481. View

19.

Hayashi T, Su T . Sigma-1 receptors (sigma(1) binding sites) form raft-like microdomains and target lipid droplets on the endoplasmic reticulum: roles in endoplasmic reticulum lipid compartmentalization and export. J Pharmacol Exp Ther. 2003; 306(2):718-25. DOI: 10.1124/jpet.103.051284. View

20.

Palmer C, Mahen R, Schnell E, Djamgoz M, Aydar E . Sigma-1 receptors bind cholesterol and remodel lipid rafts in breast cancer cell lines. Cancer Res. 2007; 67(23):11166-75. DOI: 10.1158/0008-5472.CAN-07-1771. View