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Related Experiment Videos

New methods for researching accessory proteins.

Steven M Foord1, Simon D Topp, Marco Abramo

  • 1Bioinformatics, GlaxoSmithKline, Stevenage, Herts SG1 2NY, UK. steven.m.foord@gsk.com

Journal of Molecular Neuroscience : MN
|July 14, 2005
PubMed
Summary

Receptor activity-modifying proteins (RAMPs) enable flexible signaling for peptide hormones like CGRP and adrenomedullin. Discoveries in fish and human genetics highlight RAMPs

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Area of Science:

  • Endocrinology and Molecular Pharmacology
  • G protein-coupled receptor (GPCR) signaling systems
  • Peptide hormone receptor research

Background:

  • Receptor activity-modifying proteins (RAMPs) are essential accessory proteins that modulate the function of G protein-coupled receptors (GPCRs).
  • RAMPs control the ligand specificity and cell surface expression of receptors for the calcitonin family of peptide hormones, including calcitonin, calcitonin gene-related peptide (CGRP), adrenomedullin, amylin, and adrenomedullin 2.
  • While the calcitonin receptor functions alone for calcitonin, co-expression with RAMPs enables it to bind amylin or CGRP; the calcitonin receptor-like receptor (CRLR) requires RAMPs for cell surface expression and function as a CGRP or adrenomedullin receptor.

Purpose of the Study:

  • To explore the discovery and functional significance of accessory proteins, specifically Receptor activity-modifying proteins (RAMPs), in peptide hormone receptor systems.

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  • To investigate the reasons behind the disparity between the discovery of numerous peptide ligands and fewer accessory proteins.
  • To highlight the role of modern biological techniques and comparative genomics in identifying novel ligands and accessory proteins, and the implications for human disease.

    • Main Methods:

    • Bioinformatics approaches for the discovery of seven transmembrane ligands and accessory proteins.
    • Integration of proteomics and transcriptomics to identify and experimentally validate potential accessory proteins.
    • Comparative genomics for the identification of novel peptide ligands, exemplified by adrenomedullin 2.
    • Genetic studies to elucidate the role of receptors, ligands, and accessory proteins in human diseases.

    Main Results:

    • Despite extensive research, more peptide ligands than accessory proteins have been identified, suggesting a complex regulatory landscape.
    • Bioinformatics, proteomics, transcriptomics, and comparative genomics are powerful tools for discovering new components of signaling systems.
    • The presence of multiple RAMPs in fish indicates diverse endocrinology and potentially alternative signaling mechanisms.
    • Genetic analysis provides direct insights into the involvement of these receptor-ligand-accessory protein systems in human pathophysiology.

    Conclusions:

    • Receptor activity-modifying proteins (RAMPs) are crucial for the flexible and diverse signaling of calcitonin-family peptide hormones.
    • Technological advancements are continually expanding our understanding of these complex molecular interactions.
    • The study of RAMPs and their associated receptors offers significant potential for understanding and treating human diseases.