title: G protein-induced trafficking of voltage-dependent calcium channels.
abstract: 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.
authors.affiliation: Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, New York, New York 10029, USA.
authors.forename: Eugene
authors.initials: E
authors.lastname: Tombler
authors.forename: Nory Jun
authors.initials: NJ
authors.lastname: Cabanilla
authors.forename: Paul
authors.initials: P
authors.lastname: Carman
authors.forename: Natasha
authors.initials: N
authors.lastname: Permaul
authors.forename: John J
authors.initials: JJ
authors.lastname: Hall
authors.forename: Ryan W
authors.initials: RW
authors.lastname: Richman
authors.forename: Jessica
authors.initials: J
authors.lastname: Lee
authors.forename: Jennifer
authors.initials: J
authors.lastname: Rodriguez
authors.forename: Dan P
authors.initials: DP
authors.lastname: Felsenfeld
authors.forename: Robert F
authors.initials: RF
authors.lastname: Hennigan
authors.forename: María A
authors.initials: MA
authors.lastname: Diversé-Pierluissi
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002642:Chick Embryo; D004594:Electrophysiology; D019204:GTP-Binding Proteins / Q000502:physiology*; D005727:Ganglia, Spinal / Q000502:physiology; D009475:Neurons, Afferent / Q000502:physiology*; D010446:Peptide Fragments; D020866:omega-Conotoxin GVIA / Q000494:pharmacology
chemical_list: D015220:Calcium Channels; D010446:Peptide Fragments; D020866:omega-Conotoxin GVIA; D019204:GTP-Binding Proteins