Disease relevance of Arr3

• A series of mCAR promoter-luciferase reporter constructs were transiently transfected into COS-7 or Weri-Rb-1 retinoblastoma cells and tested in in vitro promoter assays [1].

High impact information on Arr3

• We have now mimicked this TCPOBOP-dependent and OA-sensitive translocation of mouse CAR (mCAR) in HepG2 cells and have demonstrated that protein phosphatase 2A regulates this nuclear translocation [2].
• Mutation of Ser-202 to Asp (S202D) prevented mCAR translocation into the nucleus of TCPOBOP-treated HepG2 cells [2].
• GC1 and cone arrestin antibodies were used to identify photoreceptors transduced by the AAV vector and to localize cone arrestin within cone cells, respectively [3].
• Staining patterns for cone arrestin in transduced and wild-type cone cells were indistinguishable after dark and light adaptation [3].
• Light-driven cone arrestin translocation in cones of postnatal guanylate cyclase-1 knockout mouse retina treated with AAV-GC1 [3].

Biological context of Arr3

• The mCAR gene is comprised of 17 exons and 16 introns, encoding five alternatively spliced transcripts [4].
• To initiate a study of CAR's function in cone phototransduction, the mouse CAR (mCAR) transcript and protein expression patterns are examined and in vitro binding assays are also presented [5].
• Cone arrestin (CAR) is expressed in cone photoreceptors and pinealocytes and may contribute to the shutoff mechanisms associtated with high acuity color vision [5].
• METHODS: Tissue distribution of mCAR was determined by Northern and immunoblot analyses and its cellular localization identified by In situ hybridization and immunohistochemistry [5].
• In vitro binding assays show a small yet significant increase in binding of the full-length mCAR (mCARFL) to embryonic chicken OS membranes following light activation and phosphorylation of the opsins in the membranes [5].

Anatomical context of Arr3

• Mouse cone arrestin gene characterization: promoter targets expression to cone photoreceptors [4].
• The postnatal developmental expression pattern of mCAR and mSAG in the rd/rd mouse retina parallels the generation and degeneration of the cone and rod photoreceptors in these mice [5].
• In vitro binding assays with in vitro translated arrestins were used to study the interaction of mCAR and mouse S-antigen (mSAG) with embryonic chicken outer segment (OS) membranes containing both rod and cone opsins [5].
• PURPOSE: Cone arrestin (CAR) is highly expressed in all cone photoreceptors of the retina and a subset of pinealocytes in the pineal gland [1].
• Disruption of the light-driven translocation of cone arrestin is one of the phenotypes of cone cells in this retina: the cone arrestin in these cells is localized to the outer segments and synaptic terminals, regardless of the state of light adaptation [3].

Associations of Arr3 with chemical compounds

• Analysis of chimeric and mutant mCAR constructs suggested that androstenol sensitivity is controlled by residues between amino acids 201-263 (helices 5-7) and it does not depend on the residue 350 within helix 12, as previously suggested [6].

Other interactions of Arr3

• RESULTS: Translocation of cone arrestin from cone outer segments to the inner cell regions was disrupted in the absence of GC1, whereas translocation of arrestin and Talpha in rods was not affected [7].
• Nrl(-/-) photoreceptors express the mouse UV cone pigment, cone transducin, and cone arrestin in amounts expected, given the relative size and density of cones in the two retinas [8].

Analytical, diagnostic and therapeutic context of Arr3

• In situ and immunohistochemistry both reveal cone-specific expression of mCAR in the retina [5].
• The protein expression pattern of mCAR in the postnatal developmental and adult mouse retina was analyzed by immunoblotting in normal C57 and rd/rd mouse retinas [5].
• To examine whether Ser-202 can be phosphorylated, flag-tagged wild-type mCAR or flag-tagged S202A mutant was expressed in HepG2 cells and subjected to Western blot analysis using an antibody specific to a peptide containing phospho-Ser-202 [2].
• Yeast two-hybrid assays indicated that steroids inhibit mCAR primarily by promoting association of mCAR with the corepressor NCoR, with only minor contribution from other mechanisms [6].
• Immunoprecipitation with affinity-purified polyclonal antibodies against either mouse cone arrestin (mCAR) or mouse S and M cone opsins revealed specific binding of mCAR to light-activated, phosphorylated cone opsins [9].

References