Arrestin is required for agonist-induced trafficking of voltage-dependent calcium channels.
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.
Puckerin
Akil
A
Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, New York, New York 10029, USA.
Liu
Lanying
L
Permaul
Natasha
N
Carman
Paul
P
Lee
Jessica
J
Diversé-Pierluissi
María A
MA
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
D019393:Arrestin; D015220:Calcium Channels; D020864:Calcium Channels, N-Type; D010455:Peptides