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A G protein-binding domain within the α7 nicotinic receptor enables downstream calcium signaling beyond the time course of channel activation
By Justin R. King1, Ming-Kuan Lin2, Nadine Kabbani
Affiliations:
1Department of Molecular Neuroscience, Krasnow Institute for Advanced Study, George Mason University, Fairfax, VA 22030, 2INOVA Neuroscience Program, Annandale, VA 22003
Supported by the Wings for Life Spinal Cord Research Foundation
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Abstract
α7 nicotinic acetylcholine receptors (nAChRs) play an important role in synaptic transmission via regulation of intracellular signaling pathways. In recent studies, we demonstrated an important functional role for α7 nAChR interactions with intracellular heterotrimeric GTP binding proteins (G proteins) in cell signaling. Here, we show that direct coupling of the intracellular loop of the α7 receptor to Gαq enables a downstream calcium signaling response that persists beyond the time course of channel activation. This process is made possible via an evolutionary preservation of a G protein-binding cluster (GPBC) within the M3-M4 loop of nAChRs. A specific mutation of the GPBC in α7 (α7345-348A) abolishes interaction with G proteins while having no effect on the synthesis, cell-surface trafficking, or -bungarotoxin binding properties of the receptor. Expression of α7345-348A does however significantly attenuate the choline induced calcium signaling response. ...