Deactivation of phosphorylated and nonphosphorylated rhodopsin by arrestin splice variants.
Arrestins constitute a family of small cytoplasmic proteins that mediate deactivation of G-protein-coupled receptors (GPCRs) and are known to be essential for cascade inactivation and receptor desensitization. Alternative splicing produces an array of arrestin gene products that have widely different specificities for their cognate receptors in vitro, but the differential functions of these splice variants in vivo are essentially unknown. Bovine rod photoreceptors express two splice variants of visual arrestin (p44 and p48) that display different affinities for the GPCR rhodopsin. To determine the functions of these splice variants in intact cells, we expressed a transgene encoding either a truncated form of murine arrestin (mArr(1-369), or m44) or the long (p48) isoform in mouse rods lacking endogenous arrestin (Arr-/-). Morphological analysis showed that expression of either variant attenuated the light-induced degeneration that is thought to result from excessive cascade activity in Arr-/-rods. Suction electrode recordings from individual rods indicated that the expression of either m44 or p48 splice variants could restore normal kinetics to Arr-/- dim flash responses, indicating that both isoforms can bind to and quench phosphorylated rhodopsin rapidly. To our surprise, only the full-length variant was able to alter the kinetics of responses in rods lacking both arrestin and rhodopsin kinase, indicating that p48 can also quench the activity of nonphosphorylated rhodopsin.
Burns
Marie E
ME
Center for Neuroscience, Department of Psychiatry and Behavioral Sciences, University of California, Davis, California 95616, USA. meburns@ucdavis.edu
Mendez
Ana
A
Chen
Ching-Kang
CK
Almuete
Aileen
A
Quillinan
Nidia
N
Simon
Melvin I
MI
Baylor
Denis A
DA
Chen
Jeannie
J
D017398:Alternative Splicing / Q000502:physiology*; D000818:Animals; D019393:Arrestin / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D014644:Genetic Variation / Q000502:physiology*; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010766:Phosphorylation; D010775:Photic Stimulation / Q000379:methods; D012160:Retina / Q000378:metabolism; D012243:Rhodopsin / Q000235:genetics / Q000378:metabolism*
D019393:Arrestin; D012243:Rhodopsin