Title:Metabotropic Purinergic Receptors in Lipid Membrane Microdomains
Volume: 20
Issue: 1
Author(s): N. D' Ambrosi and C. Volonte
Affiliation:
Keywords:
Adenosine, caveolae, extracellular ATP, GPCR, lipid rafts, membrane microdomains, purinergic receptors, transmembrane receptors, signalling molecules, neurotransmitter
Abstract: There is broad evidence that association of transmembrane receptors and signalling molecules with lipid rafts/caveolae provides
an enriched environment for protein-protein interactions necessary for signal transduction, and a mechanism for the modulation of
neurotransmitter and/or growth factor receptor function. Several receptors translocate into submembrane compartments after ligand binding,
while others move in the opposite direction. The role of such a dynamic localization and functional facilitation is signalling modulation
and receptor desensitization or internalization. Purine and pyrimidine nucleotides have been viewed as primordial precursors in the
evolution of all forms of intercellular communication, and they are now regarded as fundamental extracellular signalling molecules. They
propagate the purinergic signalling by binding to ionotropic and metabotropic receptors expressed on the plasma membrane of almost all
cell types, tissues and organs. Here, we have illustrated the localization in lipid rafts/caveolae of G protein-coupled P1 receptors for
adenosine and P2Y receptors for nucleoside tri- and di-phosphates. We have highlighted that microdomain partitioning of these purinergic
GPCRs is cell-specific, as is the overall expression levels of these same receptors. Moreover, we have described that disruption of
submembrane compartments can shift the purinergic receptors from raft/caveolar to non-raft/non-caveolar fractions, and then abolish
their ability to activate lipid signalling pathways and to integrate with additional lipid-controlled signalling events. This modulates the
biological response to purinergic ligands and most of all indicates that the topology of the various purinergic components at the cell surface
not only organizes the signal transduction machinery, but also controls the final cellular response.
