Partners for adenosine A1 receptors.

R Franco — 2008-05-07T22:25:53-00:00

Journal of molecular neuroscience : MN, Vol. 26, No. 2-3. (2005), pp. 221-232.

G protein-coupled receptors (GPCRs) are targets for therapy in a variety of neurological diseases. Using adenosine A1 receptors (A1Rs) as paradigm of GPCRs, this review focuses on how protein-protein interactions, from monomers to heteromers, can contribute to hormone/neurotransmitter/neuromodulator regulation. The interaction of A1Rs with other membrane receptors, enzymes, and adaptor and scaffolding proteins is relevant for receptor traffic, internalization, and desensitization, and A1Rs are extremely important in driving signaling through different intracellular pathways. There is even the possibility of linking together GPCR heteromeric complexes with ion channel receptors in a receptor mosaic that might have special integrative value and might constitute the molecular basis for learning and memory.

Basic concepts in G-protein-coupled receptor homo- and heterodimerization.

R Franco — 2008-05-07T22:25:19-00:00

TheScientificWorldJournal, Vol. 7 (2007), pp. 48-57.

Until recently, heptahelical G-protein-coupled receptors (GPCRs) were considered to be expressed as monomers on the cell surface of neuronal and non-neuronal cells. It is now becoming evident that this view must be overtly changed since these receptors can form homodimers, heterodimers, and higher-order oligomers on the plasma membrane. Here we discuss some of the basics and some new concepts of receptor homo- and heteromerization. Dimers-oligomers modify pharmacology, trafficking, and signaling of receptors. First of all, GPCR dimers must be considered as the main molecules that are targeted by neurotransmitters or by drugs. Thus, binding data must be fitted to dimer-based models. In these models, it is considered that the conformational changes transmitted within the dimer molecule lead to cooperativity. Cooperativity must be taken into account in the binding of agonists-antagonists-drugs and also in the binding of the so-called allosteric modulators. Cooperativity results from the intramolecular cross-talk in the homodimer. As an intramolecular cross-talk in the heterodimer, the binding of one neurotransmitter to one receptor often affects the binding of the second neurotransmitter to the partner receptor. Coactivation of the two receptors in a heterodimer can change completely the signaling pathway triggered by the neurotransmitter as well as the trafficking of the receptors. Heterodimer-specific drugs or dual drugs able to activate the two receptors in the heterodimer simultaneously emerge as novel and promising drugs for a variety of central nervous system (CNS) therapeutic applications.

CiteULike: IrinaMoreira Casadó

Partners for adenosine A1 receptors.

Basic concepts in G-protein-coupled receptor homo- and heterodimerization.