Heterodimers and Receptor Mosaics of Different Types of G-Protein-Coupled Receptors

Physiology ◽  
2008 ◽  
Vol 23 (6) ◽  
pp. 322-332 ◽  
Author(s):  
Kjell Fuxe ◽  
Daniel Marcellino ◽  
Diego Guidolin ◽  
Amina S. Woods ◽  
Luigi F. Agnati
Keyword(s):  
Drug Development ◽  
G Protein ◽  
Research Area ◽  
G Protein Coupled Receptors ◽  
Major Research ◽  
Receptor Mosaics ◽  
Different Types ◽  
Allosteric Mechanisms ◽  
Novel Drug ◽  
G Protein Coupled

Through an assembly of interacting GPCRs, heterodimers and high-order heteromers (termed receptor mosaics) are formed and lead to changes in the agonist recognition, signaling, and trafficking of participating receptors via allosteric mechanisms, sometimes involving the appearance of cooperativity. This field has now become a major research area, and this review deals with their physiology being integrators of receptor signaling in the CNS and their use as targets for novel drug development based on their unique pharmacology.

Virally Encoded G Protein-Coupled Receptors: Targets for Potentially Innovative Anti-Viral Drug Development

2003 ◽  
Vol 4 (5) ◽  
pp. 431-441 ◽  
Author(s):  
J. Smit ◽  
C. Vink ◽  
D. Verzijl ◽  
P. Casarosa ◽  
A. Bruggeman ◽  
...  
Keyword(s):  
Drug Development ◽  
G Protein ◽  
G Protein Coupled Receptors ◽  
Virally Encoded ◽  
G Protein Coupled

Structural insights into RAMP modification of secretin family G protein-coupled receptors: implications for drug development

2011 ◽  
Vol 32 (10) ◽  
pp. 591-600 ◽  
Author(s):  
Julia K. Archbold ◽  
Jack U. Flanagan ◽  
Harriet A. Watkins ◽  
Joseph J. Gingell ◽  
Debbie L. Hay
Keyword(s):  
Drug Development ◽  
G Protein ◽  
G Protein Coupled Receptors ◽  
G Protein Coupled ◽  
Structural Insights

scholarly journals Metastable GPCR dimers trigger the basal signal by recruiting G-proteins

2020 ◽  
Author(s):  
Rinshi S. Kasai ◽  
Takahiro K. Fujiwara ◽  
Akihiro Kusumi
Keyword(s):  
G Protein ◽  
G Proteins ◽  
Single Molecule ◽  
Resting State ◽  
G Protein Coupled Receptors ◽  
Β2 Adrenergic Receptor ◽  
Low Levels ◽  
Protein Recruitment ◽  
Novel Drug ◽  
G Protein Coupled

G-protein-coupled receptors (GPCRs) constitute the largest family of integral membrane proteins in the human genome and are responsible for various important signaling pathways for vision, olfaction, gustation, emotion, cell migration, etc. A distinct feature of the GPCR-family proteins is that many GPCRs, including the prototypical GPCR, β2-adrenergic receptor (β2AR), elicit low levels of basal constitutive signals without agonist stimulation, which function in normal development and various diseases1–3. However, how the basal signals are induced is hardly known. Another general distinctive feature of GPCRs is to form metastable homo-dimers, with lifetimes on the order of 0.1 s, even in the resting state. Here, our single-molecule-based quantification4 determined the dissociation constant of β2AR homo-dimers in the PM (1.6 ± 0.29 copies/μm2) and their lifetimes (83.2 ± 6.4 ms), and furthermore found that, in the resting state, trimeric G-proteins were recruited to both β2AR monomers and homo-dimers. Importantly, inverse agonists, which suppress the GPCR’s basal constitutive activity, specifically blocked the G-protein recruitment to GPCR homo-dimers, without affecting that to monomers. These results indicate that the G-proteins recruited to transient GPCR homo-dimers are responsible for inducing their basic constitutive signals. These results suggest novel drug development strategies to enhance or suppress GPCR homo-dimer formation.

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