G Protein-induced Trafficking of Voltage-dependent Calcium Channels

• Published in: The Journal of biological chemistry Vol. 281; no. 3; pp. 1827 - 1839
• Main Authors: Tombler, Eugene, Cabanilla, Nory Jun, Carman, Paul, Permaul, Natasha, Hall, John J., Richman, Ryan W., Lee, Jessica, Rodriguez, Jennifer, Felsenfeld, Dan P., Hennigan, Robert F., Diversé-Pierluissi, María A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 20-01-2006; American Society for Biochemistry and Molecular Biology
• Subjects: Animals; Calcium Channels - drug effects; Calcium Channels - physiology; Chick Embryo; Electrophysiology; Ganglia, Spinal - physiology; GTP-Binding Proteins - physiology; Neurons, Afferent - physiology; omega-Conotoxin GVIA - pharmacology; Peptide Fragments
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M508829200

Calcium channels are well known targets for inhibition by G protein-coupled receptors, and multiple forms of inhibition have been described. Here we report a novel mechanism for G protein-mediated modulation of neuronal voltage-dependent calcium channels that involves the destabilization and subsequent removal of calcium channels from the plasma membrane. Imaging experiments in living sensory neurons show that, within seconds of receptor activation, calcium channels are cleared from the membrane and sequestered in clathrin-coated vesicles. Disruption of the L1-CAM-ankyrin B complex with the calcium channel mimics transmitter-induced trafficking of the channels, reduces calcium influx, and decreases exocytosis. Our results suggest that G protein-induced removal of plasma membrane calcium channels is a consequence of disrupting channel-cytoskeleton interactions and might represent a novel mechanism of presynaptic inhibition.