G protein-induced trafficking of voltage-dependent calcium channels.
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.
Tombler
Eugene
E
Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, New York, New York 10029, USA.
Cabanilla
Nory Jun
NJ
Carman
Paul
P
Permaul
Natasha
N
Hall
John J
JJ
Richman
Ryan W
RW
Lee
Jessica
J
Rodriguez
Jennifer
J
Felsenfeld
Dan P
DP
Hennigan
Robert F
RF
Diversé-Pierluissi
María A
MA
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
D015220:Calcium Channels; D010446:Peptide Fragments; D020866:omega-Conotoxin GVIA; D019204:GTP-Binding Proteins