Interphotoreceptor Retinoid-binding Protein

Borst, Diane E.; Redmond, T. Michael; Elser, John E.; Gonda, M A; Wiggert, Barbara; Chader, Gerald J.; Nickerson, John M.

doi:10.1016/s0021-9258(19)85061-5

Cited by 99 publications

(2 citation statements)

References 50 publications

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“…The coding sequence mFABP4 in pBluescript (provided by David Bernlohr) was subcloned into pSG-5 and pEGFP-C2. Mutant forms of FABP4 were generated by overlap extension PCR as described (41). A bacterial expression vector of histidine-tagged FABP4 was constructed by subcloning its coding sequence from pBluescript into pET28a+.…”

Section: Methodsmentioning

confidence: 99%

Continuous Nucleocytoplasmic Shuttling Underlies Transcriptional Activation of PPARγ by FABP4

et al. 2007

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FABP4 delivers specific ligands from the cytosol to the nuclear receptor PPARgamma in the nucleus, thereby facilitating the ligation and enhancing the transcriptional activity of the receptor. Here, we delineate the structural features that underlie the nucleocytoplasmic transport of FABP4. The primary sequence of FABP4 does not harbor a readily identifiable nuclear localization signal (NLS). However, such a signal could be found in the three-dimensional structure of the protein and was mapped to three basic residues that form a functional NLS stabilized by the FABP4/PPARgamma ligand troglitazone. We show that FABP4 is also subject to active nuclear export. Similarly to the NLS, the nuclear export signal (NES) is not apparent in the primary sequence, but assembles in the tertiary structure from three nonadjacent leucine residues to form a motif reminiscent of established NES. The data demonstrate that both nuclear export and nuclear import are critical for enabling FABP4 to enhance the transcriptional activity of PPARgamma. Additionally, the observations provide insight into the fundamental question of how proteins are activated by ligands. Such an activation may be understood by the "induced-fit" model, which states that ligand-induced conformational changes precede activation of a protein. Alternatively, the "pre-existing equilibrium" hypothesis postulates that activated conformations exist within the repertoire of apoproteins, and that ligands do not induce these but merely stabilize them. Studies of the subcellular localization of FABP4 support the validity of the "pre-existing equilibrium" model for the ligand-controlled activation of the nuclear import of FABP4.

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Section: Methodsmentioning

confidence: 99%

Continuous Nucleocytoplasmic Shuttling Underlies Transcriptional Activation of PPARγ by FABP4

et al. 2007

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“…1990), primers for (CT)23 upstream non-coding repeat were designed in our laboratory. bBOVIRBP = DNA sequence of bovine interphotoreceptor retinoid-binding protein gene (published by Liou et al 1986;Borst et al 1989). Primers were designed and donated by D. MacHugh (Department of Genetics, Trinity College Dublin).…”

Section: (E) a N A Ly Sis O F S U R V Iv A Lmentioning

confidence: 99%

Molecular genetic variation and individual survival during population crashes of an unmanaged ungulate population

Bancroft

Pemberton

Albon³

et al. 1995

Phil. Trans. R. Soc. Lond. B

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Theoretical models of the effect of population bottlenecks on genetic variation assume that individuals are removed at random from the population. We investigated this assumption in a naturally regulated, unstable population of Soay sheep (Ovis aries). During rapid population declines or 'crashes', individuals were not removed at random with respect to genotype: we found associations between individual survival and certain genotypes at five polymorphic protein or microsatellite DNA loci (Ada, Got, Tf, MAF18 and OPACAP). Some loci appeared to show simple associations with survival whereas others had more complex interactions with crash year or age: all displayed different patterns of association between the sexes. Simple overdominance was not a general feature of our data; it seems likely that fluctuating selecting, countervailing selection in different fitness components or frequency-dependent selection may explain the pattern and complexity of the associations shown at different loci. Our study cannot distinguish between selection acting at these loci or at other, closely linked loci. However, our empirical study implies that the molecular genetic outcome of population bottlenecks in natural populations does not always follow theoretical expectations based on the random removal of genotypes. Bottlenecks in which individuals are removed at random are distinct from bottlenecks in which there is scope for selection via non-random survival of individuals.

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Suppression of spontaneous uveoretinitis development by non-immunopathogenic peptide immunization

et al. 1998

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BALB/c nude mice which are grafted with thymus tissue from fetal F344 rats beneath the renal capsule (hereafter referred to as TG nude mice) spontaneously develop uveoretinitis as well as other organ-localized autoimmune diseases. Active immunization with an interphotoreceptor retinoid-binding protein (IRBP)-derived peptide, amino acids 518-529 (P518-529), induced rapid development and high incidence of uveoretinitis, whereas immunization with another amino acid fragment, 1182-1194 (P1182-1194), inhibited the disease process. P1182-1194- or P518-529-specific T cell lines were established from TG nude mice. Although both were of CD4+ type, P518-529-specific T cells expressed Vbeta8 TCR while Vbeta6 expression was evident in the P1182-1194-specific cells. P518-529-specific T cells produced IL-2 and IFN-gamma, but not IL-4 or IL-10, whereas P1182-1194-specific T cells produced IL-4 and IL-10, but not IL-2 or IFN-gamma Adoptive transfer of these peptide-specific T cells into naive BALB/c nude mice resulted in development of uveoretinitis only in the P518-529 case. Furthermore, mice receiving both T cell types simultaneously did not exhibit uveoretinitis. The results indicate that the amino acid fragment of IRBP, P518-529, is uveitogenic and immunogenic in TG nude mice and induces Th1-type T cells related to uveoretinitis, whereas the amino acid fragment 1182-1194 is immunogenic but not uveitogenic, inducing Th2-type T cells which are involved in inhibition of this pathological response in TG nude mice.

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Interphotoreceptor Retinoid-binding Protein

Cited by 99 publications

References 50 publications

Continuous Nucleocytoplasmic Shuttling Underlies Transcriptional Activation of PPARγ by FABP4

Continuous Nucleocytoplasmic Shuttling Underlies Transcriptional Activation of PPARγ by FABP4

Molecular genetic variation and individual survival during population crashes of an unmanaged ungulate population

Suppression of spontaneous uveoretinitis development by non-immunopathogenic peptide immunization

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