In receptor biology, heteromerisation often occurs between G protein-coupled receptors (GPCRs), a large family of membrane proteins that mediate cellular responses to external stimuli. When two different GPCRs interact, they can form heteromers that exhibit unique pharmacological properties, signaling pathways, or tissue-specific distributions compared to their individual components. For example, the dopamine D2 receptor and the serotonin 5-HT1A receptor can heteromerise, influencing neurotransmitter signaling in the brain. These complexes may also alter drug binding affinities, potentially explaining variations in therapeutic responses or side effects.
Heteromerisation is not limited to GPCRs; it also plays a role in ion channels, such as those formed by combinations of voltage-gated calcium channels or NMDA receptors, where subunit interactions fine-tune channel properties like conductance, gating kinetics, or pharmacological sensitivity. In enzymatic systems, heteromeric complexes, such as certain kinases or phosphatases, can integrate multiple regulatory inputs, enhancing cellular control over metabolic or signaling pathways.
The study of heteromerisation has gained traction due to its implications in physiology and disease. Dysregulation of heteromeric complexes has been linked to conditions like neurodegenerative disorders, cardiovascular diseases, and psychiatric illnesses. Understanding these interactions offers potential targets for drug development, as heteromers may provide more selective or effective therapeutic interventions compared to targeting individual subunits.
Experimental techniques, including co-immunoprecipitation, bioluminescence resonance energy transfer (BRET), and cryo-electron microscopy, have been instrumental in identifying and characterizing heteromeric protein assemblies. Ongoing research continues to elucidate the structural and functional dynamics of these complexes, expanding our knowledge of cellular communication and disease mechanisms.