Skip to main content

Subcellular Localization and Interacellular Dynamics of σ1 Receptors

  • Chapter

5. Conclusions

Recent studies using specific ol receptor antibodies, in corroboration with early subcellular fractionation studies, begin to unveil the unique cellular localization of σ1 receptors. It is clear now that σ1 receptors localize predominantly on the ER in varieties of mammalian cells, although σ1 receptors can show a multi-organelle distribution pattern inside the cell. Details of σ1 receptor distribution in highly polarized neurons in the brain will be examined in future studies. Understanding the protein topology and lipid components of specific membrane domains where σ1 receptors target (eg. lipid-rich globules on the ER) must help to unveil the exact molecular mechanism of σ1 receptors. ol Receptors show a very unique ability to translocate that is evoked by varieties of psychotropic drugs possessing σ1 receptor affinities. The dynamics of σ1 receptors appears to be related intimately to diverse actions exerted by σ1 ligands, particularly at the plasma membrane and at the ER. These actions include regulations of channel activity, exocytosis, signal transduction, plasma membrane remodeling (raft formation), and lipid transport/metabolism. All these actions may have a bearing in promoting neuronal plasticity in the brain.

This is a preview of subscription content, log in via an institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Alonso G, Phan V, Guillemain I, Saunier M, Legrand A, Anoal M, Maurice T. Immunocytochemical localization of the a, receptor in the adult rat central nervous system. Neuroscience 2000, 97: 155–170.

    Article  PubMed  CAS  Google Scholar 

  2. Aydar E, Palmer CP, Klyachko VA, Jackson MB. The a receptor as a ligand-regulated auxiliary potassium channel subunit. Neuron 2002, 34:399–410.

    Article  PubMed  CAS  Google Scholar 

  3. Basile AS, Paul IA, de Costa B. Differential effects of cytochrome P-450 induction on ligand binding to a receptors. Eur J Pharmacol 1992, 227:95–98.

    Article  PubMed  CAS  Google Scholar 

  4. Cagnotto A, Bastone A, Mennini T. [3H](+)-pentazocine binding to rat brain σ1 receptors. Eur J Pharmacol 1994, 266:131–138.

    Article  PubMed  CAS  Google Scholar 

  5. De Haven-Hudkins DL, Lanyon LF, Ford-Rice FY, Ator MA. Sigma recognition sites in brain and peripheral tissues. Characterization and effects of cytochrome P450 inhibitors. Biochem Pharmacol 1994, 47:1231–1239.

    Article  Google Scholar 

  6. Demerens C, Stankoff B, Zalc B, Lubetzki C. Eliprodil stimulates CNS myelination: new prospects for multiple sclerosis? Neurology 1999, 52:346–350.

    PubMed  CAS  Google Scholar 

  7. Dussossoy D, Carayon P, Belugou S, Feraut D, Bord A, Goubet C, Roque C, Vidal H, Combes T, Loison G, Casellas P. Colocalization of sterol isomerase and σ1 receptor at endoplasmic reticulum and nuclear envelope level. Eur J Biochem 1999, 263:377–386.

    Article  PubMed  CAS  Google Scholar 

  8. Hanner M, Moebius FF, Flandorfer A, Knaus HG, Striessnig J, Kempner E, Glossmann H. Purification, molecular cloning, and expression of the mammalian a,-binding site. Proc Natl Acad Sci USA 1996, 93:8072–8077.

    Article  PubMed  CAS  Google Scholar 

  9. Hayashi T, Maurice T, Su TP. Ca2+ signaling via σ1 receptors: novel regulatory mechanism affecting intracellular Ca2+ concentration. J Pharmacol Exp Ther 2000, 293:788–798.

    PubMed  CAS  Google Scholar 

  10. Hayashi T, Su TP. Regulating ankyrin dynamics: Roles of σ1 receptors. Proc Natl Acad Sci USA 2001, 98:491–496.

    Article  PubMed  CAS  Google Scholar 

  11. Hayashi T, Su TP. Sigma-1 receptors form raft-like microdomains and target lipid droplets on the endoplasmic reticulum (ER): roles in ER lipid compartmentalization and export. J Pharmacol Exp Ther 2003% 306:718–725.

    Article  PubMed  CAS  Google Scholar 

  12. Hayashi T, Su TP. Intracellular dynamics of o1 receptors in NG108-15 cells. J Pharmacol Exp Ther 2003b, 306:726–733.

    Article  PubMed  CAS  Google Scholar 

  13. Hayashi T, Su TP. Sigma-1 receptors at galactosylceramide-enriched lipid microdomains regulate oligodendrocyte differentiation. Proc Natl Acad Sci USA 2004, 101: 14949–14954.

    Article  PubMed  CAS  Google Scholar 

  14. Itzhak Y, Stein I, Zhang SH, Kassim CO, Cristante D. Binding of a-ligands to C57BL16 mouse brain membranes: effects of monoamine oxidase inhibitors and subcellular distribution studies suggest the existence of a-receptor subtypes. J Pharmacol Exp Ther 1991, 257:141–148.

    PubMed  CAS  Google Scholar 

  15. Jbilo 0, Vidal H, Paul R, De Nys N, Bensaid M, Silve S, Carayon P, Davi D, Galiegue S, Bourrie B, Guillemot JC, Ferrara P, Loison G, Maffrand JP, Le Fur G, Casellas P. Purification and characterization of the human SR 31747A-binding protein. A nuclear membrane protein related to yeast sterol isomerase. J Biol Chem 1997, 272:27107–27115.

    Article  PubMed  CAS  Google Scholar 

  16. Kekuda R, Prasad PD, Fei YJ, Leibach FH, Ganapathy V. Cloning and functional expression of the human type 1 σ receptor (hSigmaR1). Biochem Biophys Res Commun 1996, 229553–558.

    Article  PubMed  CAS  Google Scholar 

  17. McCann DJ, Rabin RA, Rens-Domiano S, Winter JC. PhencyclidineISKF-10,047 binding sites: evaluation of function. Pharmacol Biochem Behav 1989, 32:87–94.

    Article  PubMed  CAS  Google Scholar 

  18. McCann DJ, Su TP. Haloperidol-sensitive (+)[3H]sKF-10,047 binding sites (o sites) exhibit a unique distribution in rat brain subcellular fractions. Eur J Pharmacol 1990;188:211–218.

    Article  PubMed  CAS  Google Scholar 

  19. McCann DJ, Weissman AD, Su TP. Sigma-1 and o2 sites in rat brain: comparison of regional, ontogenetic, and subcellular patterns. Synapse 1994, 17: 182–189.

    Article  PubMed  CAS  Google Scholar 

  20. Morin-Surun MP, Collin T, Denavit-Saubie M, Baulieu EE, Monnet FP. Intracellular σ1 receptor modulates phospholipase C and protein kinase C activities in the brainstem. Proc Natl Acad Sci USA 1999, 96:8196–8199.

    Article  PubMed  CAS  Google Scholar 

  21. Night AR, Noble A, Wong EHF, Middlemiss DN. The subcellular distribution and pharmacology of the sigma recognition site in the guinea-pig brain and liver. Mol Neuropharmacol 1991, 1:77–82.

    Google Scholar 

  22. Palacios G, Muro A, Vela JM, Molina-Holgado E, Guitart X, Ovalle S, Zamanillo D. Immunohistochemical localization of the ol-receptor in oligodendrocytes in the rat central nervous system. Brain Res 2003, 961:92–99.

    Article  PubMed  CAS  Google Scholar 

  23. Ramamoorthy JD, Ramamoorthy S, Mahesh VB, Leibach FH, Ganapathy V. Cocainesensitive o-receptor and its interaction with steroid hormones in the human placental syncytiotrophoblast and in choriocarcinoma cells. Endocrinology 1995, 136:924–932.

    Article  PubMed  CAS  Google Scholar 

  24. Samovilova NN, Vinogradov VA. Subcellular distribution of (+)-[3H]sKF 10,047 binding sites in rat liver. Eur J Pharmacol 1992, 225:69–74.

    Article  PubMed  CAS  Google Scholar 

  25. Schutze MP, Peterson PA, Jackson MR. An N-terminal double-arginine motif maintains type I1 membrane proteins in the endoplasmic reticulum. EMBO J 1994, 13:1696–1705.

    PubMed  CAS  Google Scholar 

  26. Seth P, Leibach FH, Ganapathy V. Cloning and structural analysis of the cDNA and the gene encoding the murine type 1 σ receptor. Biochem Biophys Res Commun 1997, 241:535–540.

    Article  PubMed  CAS  Google Scholar 

  27. Seth P, Fei YJ, Li HW, Huang W, Leibach FH, Ganapathy V. Cloning and functional characterization of a σ receptor from rat brain. J Neurochem 1998, 70:922–931.

    Article  PubMed  CAS  Google Scholar 

  28. Shamsul Ola M, Moore P, El-Sherbeny A, Roon P, Agarwal N, Sarthy VP, Casellas P, Ganapathy V, Smith SB. Expression pattern of σ receptor 1 mRNA and protein in mammalian retina. Brain Res Mol Brain Res 2001, 95:86–95.

    Article  CAS  Google Scholar 

  29. Simons K, Toomre D. Lipid rafts and signal transduction. Nat Rev Mol Cell Biol 2001, l:3 1–39

    Google Scholar 

  30. Simony-Lafontaine J, Esslimani M, Bribes E, Gourgou S, Lequeux N, Lavail R, Grenier J, Kramar A, Casellas P. Immunocytochemical assessment of σ1 receptor and human sterol isomerase in breast cancer and their relationship with a series of prognostic factors. Br J Cancer 2000, 82: 1958–1966.

    Article  PubMed  CAS  Google Scholar 

  31. Spacek J, Harris KM. Three-dimensional organization of smooth endoplasmic reticulum in hippocampal CAI dendrites and dendritic spines of the immature and mature rat. J Neurosci 1997, 17: 190–203.

    PubMed  CAS  Google Scholar 

  32. Su TP, Hayashi T. Cocaine affects the dynamics of cytoskeletal proteins via σ1 receptors. Trends Pharmacol Sci 2001, 22:456–458.

    Article  PubMed  CAS  Google Scholar 

  33. Takebayashi M, Hayashi T, Su TP. Sigma-1 receptors potentiate epidermal growth factor signaling towards neuritegenesis in PC12 cells: potential relation to lipid raft reconstitution. Synapse 2004, 53:90–103.

    Article  PubMed  CAS  Google Scholar 

  34. Tanaka M, Shirasaki T, Kaku S, Muramatsu M, Otomo S. Characteristics of binding of [3H]NE-100, a novel sigma-receptor ligand, to guinea-pig brain membranes. Naunyn Schmiedeberg Arch Pharmacol 1995, 351:244–251.

    CAS  Google Scholar 

  35. Yamamoto H, Miura R, Yamamoto T, Shinohara K, Watanabe M, Okuyama S, Nakazato A, Nukada T. Amino acid residues in the transmembrane domain of the type 1 σ receptor critical for ligand binding. FEBS Lett 1999, 445:19–22.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Teruo Hayashi .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2007 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Hayashi, T., Su, TP. (2007). Subcellular Localization and Interacellular Dynamics of σ1 Receptors. In: Su, TP., Matsumoto, R.R., Bowen, W.D. (eds) Sigma Receptors. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-36514-5_8

Download citation

Publish with us

Policies and ethics