GPCR Oligomeric Receptor Complexes and Their Role in the Integration of Signals in Space and Time

Dear Colleagues,

GPCRs not only exist as monomers but also as homomers and heteromers in which allosteric receptor–receptor interactions take place modulating the functions of the participating GPCR protomers. GPCRs can also form heteroreceptor complexes with ionotropic receptors and receptor tyrosine kinases modulating their function. Furthermore, adaptor proteins interact with receptor protomers and modulate the interactions. The state of the art is that the allosteric receptor–receptor interactions are reciprocal, highly dynamic and substantially alter the signaling, trafficking, recognition and pharmacology of the participating protomers in space and time. The pattern of changes appears to be unique for each heteromer and can favor antagonistic or facilitatory interactions or switch the G protein coupling from, e.g., Gi/o to Gq or to beta-arrestin signaling. It gives a new dimension to molecular integration in the nervous system. The future direction should be to determine their brain distribution and selective cell populations (e.g., neurons, astrocytes, oligodendrocytes) where they are expressed. Additionally, their balance mechanisms function on time. This will help determine in depth details regarding the functional role of the allosteric receptor–receptor interaction versus integration of the intracellular signaling pathways in the function of the receptor heterodimer. Integration of signals already at the plasma membrane seems crucial when considering the hypothesis that learning and memory at the molecular level takes place through reorganization of homo- and heteroreceptor complexes in the postsynaptic membrane. Homo- and heteroreceptor complexes are in balance with each other, and their disbalance is linked to various diseases. Targeting heteroreceptor complexes represents a novel strategy for treatment of brain disorders.

For this Special Issue, we invite researchers to contribute original research articles and reviews on all aspects related to GPCR oligomeric receptor complexes.

Dr. Dasiel O. Borroto Escuela
Dr. Michael Di Palma
Dr. Ramon Fores-Pons
Guest Editors

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• G protein-coupled receptors
• oligomerization
• receptor-receptor interaction
• signal integration
• allosteric interactions
• heteroreceptor complexes