title: Arrestin is required for agonist-induced trafficking of voltage-dependent calcium channels.
abstract: Many metabotropic receptors in the nervous system act through signaling pathways that result in the inhibition of voltage-dependent calcium channels. Our previous findings showed that activation of seven-transmembrane receptors results in the internalization of calcium channels. This internalization takes place within a few seconds, raising the question of whether the endocytic machinery is in close proximity to the calcium channel to cause such rapid internalization. Here we show that voltage-dependent calcium channels are pre-associated with arrestin, a protein known to play a role in receptor trafficking. Upon GABAB receptor activation, receptors are recruited to the arrestin-channel complex and internalized. beta-Arrestin 1 selectively binds to the SNARE-binding region of the calcium channel. Peptides containing the arrestin-binding site of the channel disrupt agonist-induced channel internalization. Taken together these data suggest a novel neuronal role for arrestin.
authors.affiliation: Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, New York, New York 10029, USA.
authors.forename: Akil
authors.initials: A
authors.lastname: Puckerin
authors.forename: Lanying
authors.initials: L
authors.lastname: Liu
authors.forename: Natasha
authors.initials: N
authors.lastname: Permaul
authors.forename: Paul
authors.initials: P
authors.lastname: Carman
authors.forename: Jessica
authors.initials: J
authors.lastname: Lee
authors.forename: María A
authors.initials: MA
authors.lastname: Diversé-Pierluissi
mesh_terms: D000818:Animals; D019393:Arrestin / Q000378:metabolism / Q000502:physiology*; D001665:Binding Sites; D015220:Calcium Channels / Q000378:metabolism*; D020864:Calcium Channels, N-Type / Q000378:metabolism; D002642:Chick Embryo; D004705:Endocytosis; D009474:Neurons / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D021381:Protein Transport; D015398:Signal Transduction
chemical_list: D019393:Arrestin; D015220:Calcium Channels; D020864:Calcium Channels, N-Type; D010455:Peptides