Disease relevance of Arr1

• Flies carrying each of these alleles underwent light-dependent retinal degeneration and displayed electrophysiological defects typical of previously identified arrestin mutants, including an allele encoding a protein that lacks the major Ca2+/calmodulin-dependent protein kinase site [1].
• We propose that the sequestering of arrestin to membranes is a possible mechanism for retinal disease associated with previously identified rhodopsin alleles in humans [1].

High impact information on Arr1

• In this paper, we develop a theory that describes the kinetics of inactivation of the G protein-coupled receptor rhodopsin based on the rate of arrestin binding and test the theory using a combination of genetic and electrophysiological techniques in Drosophila photoreceptors [2].
• The results demonstrate that the rate of arrestin binding determines the kinetics of receptor inactivation in vivo and thus is the event that controls signal amplification at the first step of this G protein-coupled transduction cascade [2].
• Analysis of the light response in these mutants shows that the Arr1 and Arr2 proteins are mediators of rhodopsin inactivation and are essential for the termination of the phototransduction cascade in vivo [3].
• A role for the light-dependent phosphorylation of visual arrestin [1].
• This proposal is supported by the finding that rhodopsin 2 and arrestin 1, two photoreceptor-cell-specific genes, are also expressed in male gonads [4].

Biological context of Arr1

• We further find that Rh1 C-terminal phosphorylation is essential for light-induced endocytosis and also for translocation of Arr1, but not Arr2, from dark-adapted photoreceptor cytoplasm to photosensory membrane rhabdomeres [5].
• RESULTS: We report that Arr1, but not Arr2, is essential for normal, light-induced rhodopsin endocytosis [5].
• Photoreceptor cell death caused by loss of Arr1 is strongly suppressed by coordinate loss of Arr2 [5].
• Arrestin mutant phenotypes are hypothesized to be a consequence of down-regulation of olfactory signaling to avoid cellular excitotoxicity [6].
• This gene encodes a 364-amino acid protein that displays greater than 40% amino acid sequence identity with human and bovine arrestin [7].

Anatomical context of Arr1

• CONCLUSIONS: These results indicate that rhodopsin and arrestin protein synthesis in Drosophila photoreceptors do not fluctuate on a daily cycle [8].
• The loss of immunoreactive rhabdomeric rhodopsin only occurred when rhodopsin was depleted from the plasma membrane such that it was found within the rhabdomere at stoichiometric levels with arrestin [9].

Associations of Arr1 with chemical compounds

• However, the arrestin gene does not appear to be the ninaD locus, as sequence analysis of three ethylmethane sulfate-induced ninaD mutant alleles reveals no alteration in amino acid sequence [7].
• New work has identified a phosphoinositide lipid binding domain in Drosophila arrestin and implicates PIP(3) in control of arrestin translocation [10].

Other interactions of Arr1

• Exploratory Activity in Drosophila Requires the kurtz Nonvisual Arrestin [11].

Analytical, diagnostic and therapeutic context of Arr1

• Proteins were resolved by polyacrylamide gel electrophoresis (PAGE) and subjected to immunoblot analysis using antibodies directed to rhodopsin, NinaA, Arr1, and Arr2 [8].
• (2) Rabbit antibodies raised against Musca PRI, against bovine arrestin, and against a synthetic peptide based on the Drosophila PRI sequence stained the Drosophila and Musca PRIs specifically on 1 and 2-dimensional Western immunoblots [12].
• One of these clones has been identified, by sequence analysis, as the structural gene (Arr) for a Drosophila homolog of human arrestin [13].
• 1 microm frozen sections were cut on an ultracryomicrotome, then stained with antibodies specific for rhodopsin or arrestin [9].

References