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Functional Rescue of Misfolded Receptor Mutants

  • Conference paper
Insights into Receptor Function and New Drug Development Targets

Part of the book series: Research and Perspectives in Endocrine Interactions ((RPEI))

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Summary

Mutant gonadotropin-releasing hormone (GnRH) receptors isolated from patients with GnRH-resistant hypogonadotropic hypogonadism are frequently proteins that are misrouted in the cell. Such mutant receptors are retained in the endoplasmic reticulum and can be rescued by pharmacological chaperones. This understanding contrasts with the view that these mutant receptors lose the ability to bind ligand or effect signal transduction. Pharmacological chaperones, or “pharmacoperones,” bind specifically to GnRH receptors and allow them to escape retention by the cellular quality control systems and route to the plasma membrane, where they function normally. This observation suggests that pharmacoperones have the potential to be used to treat a number of human diseases characterized by misrouted proteins, among these, hypogonadotropic hypogonadism, cystic fibrosis and nephrogenic diabetes insipidus.

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Author information

Authors and Affiliations

  1. Division of Neuroscience, Oregon National Primate Research Center, USA

    Shaun P. Brothers & P. Michael Conn

  2. Division of Reproductive Biology, Oregon National Primate Research Center, USA

    P. Michael Conn

  3. Department of Physiology and Pharmacology, Oregon Health and Science University, USA

    Shaun P. Brothers & P. Michael Conn

  4. Department of Cell and Developmental Biology, Oregon Health and Science University, USA

    P. Michael Conn

Authors
  1. Shaun P. Brothers
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  2. P. Michael Conn
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Editor information

Editors and Affiliations

  1. Divisions of Neuroscience and Reproductive Biology, Departments of Physiology and Pharmacology and Cell and Developmental Biology, Oregon National Primate Research Center, Oregon Health and Science University, 505 NW 185th Avenue, Beaverton, Oregon, 97006, USA

    Michael Conn Ph.D.

  2. Institut Necker, 156, rue de Vaugirard, 75015, Paris, France

    Claude Kordon Ph.D.

  3. Pour la Recherche Thérapeutique, Fondation IPSEN, 24, rue Erlanger, 75781, Paris Cedex 16, France

    Yves Christen Ph.D.

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© 2006 Springer-Verlag Berlin Heidelberg

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Brothers, S.P., Conn, P.M. (2006). Functional Rescue of Misfolded Receptor Mutants. In: Conn, M., Kordon, C., Christen, Y. (eds) Insights into Receptor Function and New Drug Development Targets. Research and Perspectives in Endocrine Interactions. Springer, Berlin, Heidelberg . https://doi.org/10.1007/3-540-34447-0_2

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