Beta-adrenergic receptor kinase-2 and beta-arrestin-2 as mediators of odorant-induced desensitization.
beta-Adrenergic receptor kinase (beta ARK) and beta-arrestin function in the homologous or agonist-activated desensitization of G protein-coupled receptors. The isoforms beta ARK-2 and beta-arrestin-2 are highly enriched in and localized to the dendritic knobs and cilia of the olfactory receptor neurons where the initial events of olfactory signal transduction occur. Odorants induce a rapid and transient elevation of adenosine 3',5'-monophosphate (cAMP), which activates a nonspecific cation channel and produces membrane depolarization. Preincubation of rat olfactory cilia with antibodies raised against beta ARK-2 and beta-arrestin-2 increased the odorant-induced elevation of cAMP and attenuated desensitization. These results suggest that beta ARK-2 and beta-arrestin-2 mediate agonist-dependent desensitization in olfaction.
Department of Neuroscience, Johns Hopkins Medical Institutions, Baltimore, MD 21205.
T M
TM
Dawson
J L
JL
Arriza
D E
DE
Jaworsky
F F
FF
Borisy
H
H
Attramadal
R J
RJ
Lefkowitz
G V
GV
Ronnett
D000818:Animals; D000941:Antigens / Q000378:metabolism*; D019390:Arrestins; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases; D003600:Cytosol / Q000378:metabolism; D003712:Dendrites / Q000502:physiology; D005136:Eye Proteins / Q000378:metabolism*; D054769:G-Protein-Coupled Receptor Kinase 2; D019204:GTP-Binding Proteins / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D008465:Mechanoreceptors / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D009812:Odorants; D009830:Olfactory Bulb / Q000502:physiology*; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D015398:Signal Transduction; D012903:Smell; D013737:Testis / Q000502:physiology; D014420:Turbinates / Q000502:physiology*; D051552:beta-Adrenergic Receptor Kinases; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins
D000941:Antigens; C000605257:Arrb2 protein, rat; D019390:Arrestins; D005136:Eye Proteins; D007527:Isoenzymes; D011943:Receptors, Adrenergic, beta; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins; D000242:Cyclic AMP; D011494:Protein Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; C496569:Grk2 protein, rat; D051552:beta-Adrenergic Receptor Kinases; D054769:G-Protein-Coupled Receptor Kinase 2; D019204:GTP-Binding Proteins