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D Stephen Serafin1, Natalie R Harris1, Natalie R Nielsen1
1Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Trends in Pharmacological Sciences
|March 3, 2020
Summary
Receptor activity-modifying proteins (RAMPs) interact with G-protein-coupled receptors (GPCRs), revealing new therapeutic targets. These novel RAMP-GPCR interactions offer potential for developing innovative drugs for various human pathologies.
Area of Science:
- Molecular biology
- Pharmacology
- Biochemistry
Background:
- Receptor activity-modifying proteins (RAMPs) are crucial regulators of G-protein-coupled receptor (GPCR) function.
- RAMP-GPCR interactions significantly influence physiological processes and therapeutic strategies.
- Recent advancements in coevolution studies and screening platforms have renewed interest in identifying these interactions.
Purpose of the Study:
- To highlight novel RAMP-GPCR interactions beyond Class B GPCRs.
- To review human RAMP-GPCR disease-causing mutations and RAMP-related pathologies.
- To underscore the potential for RAMP-targeted drug development.
Main Methods:
- Coevolution studies.
- Orthogonal technological screening platforms.
- Literature review of recent publications.
Main Results:
- Identification of previously unrecognized RAMP-interacting GPCRs, extending beyond Class B.
- Uncovered novel RAMP-GPCR interactions.
- Documented human RAMP-GPCR disease-causing mutations and RAMP-related pathologies.
Conclusions:
- Novel RAMP-GPCR interactions provide a foundation for new molecular therapeutic targets.
- The success of drugs like erenumab exemplifies the therapeutic potential of targeting RAMP-GPCRs.
- This research paves the way for a new era of RAMP-targeted drug development.
