Coupling ion channels to receptors for biomolecule sensing.
Nanoscale electrical biosensors are promising tools for diagnostics and high-throughput screening systems. The electrical signal allows label-free assays with a high signal-to-noise ratio and fast real-time measurements. The challenge in developing such biosensors lies in functionally connecting a molecule detector to an electrical switch. Advances in this field have relied on synthetic ion-conducting pores and modified ion channels that are not yet suitable for biomolecule screening. Here we report the design and characterization of a novel bioelectric-sensing platform engineered by coupling an ion channel, which serves as the electrical probe, to G-protein-coupled receptors (GPCRs), a family of receptors that detect molecules outside the cell. These ion-channel-coupled receptors may potentially detect a wide range of ligands recognized by natural or altered GPCRs, which are known to be major pharmaceutical targets. This could form a unique platform for label-free drug screening.
Laboratoire des Protéines Membranaires, Institut de Biologie Structurale (CEA, CNRS, UJF), 41 rue Jules Horowitz, 38027 Grenoble, France.
Christophe J
CJ
Moreau
Julien P
JP
Dupuis
Jean
J
Revilloud
Karthik
K
Arumugam
Michel
M
Vivaudou
D000818:Animals; D015374:Biosensing Techniques / Q000379:methods*; D065127:Dopamine D2 Receptor Antagonists; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004553:Electric Conductivity; D006801:Humans; D017136:Ion Transport / Q000187:drug effects; D008024:Ligands; D051379:Mice; D046912:Multiprotein Complexes / Q000235:genetics* / Q000378:metabolism*; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics / Q000378:metabolism; D015202:Protein Engineering / Q000379:methods*; D043585:Receptor, Muscarinic M2 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000235:genetics* / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D000099161:Kcnj11 Channel
D065127:Dopamine D2 Receptor Antagonists; D008024:Ligands; D046912:Multiprotein Complexes; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D043585:Receptor, Muscarinic M2; D017448:Receptors, Dopamine D2; D011993:Recombinant Fusion Proteins; D000099161:Kcnj11 Channel