Direct binding of visual arrestin to microtubules determines the differential subcellular localization of its splice variants in rod photoreceptors.
Proper function of visual arrestin is indispensable for rapid signal shut-off in rod photoreceptors. Dramatic light-dependent changes in its subcellular localization are believed to play an important role in light adaptation of photoreceptor cells. Here we show that visual arrestin binds microtubules. The truncated splice variant of visual arrestin, p44, demonstrates dramatically higher affinity for microtubules than the full-length protein (p48). Enhanced microtubule binding of p44 underlies its earlier reported preferential localization to detergent-resistant membranes, where it is anchored via membrane-associated microtubules in a rhodopsin-independent fashion. Experiments with purified proteins demonstrate that arrestin interaction with microtubules is direct and does not require any additional protein partners. Most importantly, arrestin interactions with microtubules and light-activated phosphorylated rhodopsin are mutually exclusive, suggesting that microtubule interaction may play a role in keeping p44 arrestin away from rhodopsin in dark-adapted photoreceptors.
Department of Molecular and Cellular Pharmacology and Neuroscience Program, University of Miami, Miami, Florida 33136, USA.
K Saidas
KS
Nair
Susan M
SM
Hanson
Matthew J
MJ
Kennedy
James B
JB
Hurley
Vsevolod V
VV
Gurevich
Vladlen Z
VZ
Slepak
D017398:Alternative Splicing; D000818:Animals; D019393:Arrestin / Q000737:chemistry / Q000378:metabolism; D019390:Arrestins / Q000737:chemistry* / Q000378:metabolism; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D002499:Centrifugation, Density Gradient; D002846:Chromatography, Affinity; D002853:Chromatography, Liquid; D003599:Cytoskeleton / Q000378:metabolism; D003902:Detergents / Q000494:pharmacology; D004926:Escherichia coli / Q000378:metabolism; D008027:Light; D013058:Mass Spectrometry; D021962:Membrane Microdomains; D008870:Microtubules / Q000378:metabolism*; D008969:Molecular Sequence Data; D010766:Phosphorylation; D010786:Photoreceptor Cells / Q000378:metabolism; D011485:Protein Binding; D011994:Recombinant Proteins / Q000737:chemistry; D012160:Retina / Q000378:metabolism; D012374:Rod Cell Outer Segment / Q000378:metabolism; D013395:Sucrose / Q000737:chemistry / Q000494:pharmacology; D013997:Time Factors
D019393:Arrestin; D019390:Arrestins; D003902:Detergents; D011994:Recombinant Proteins; D013395:Sucrose