The Experts below are selected from a list of 7407 Experts worldwide ranked by ideXlab platform
James B. Hurley - One of the best experts on this subject based on the ideXlab platform.
-
mapping sites in guanylyl cyclase activating protein 1 required for regulation of Photoreceptor Membrane guanylyl cyclases
Journal of Biological Chemistry, 1999Co-Authors: Dmitri M Krylov, Alexander M. Dizhoor, Gregory A Niemi, James B. HurleyAbstract:Guanylyl cyclase activating protein (GCAP)-1 regulates Photoreceptor Membrane guanylyl cyclase, RetGC, in a Ca2+-sensitive manner. It contains four Ca2+-binding motifs, EF-hands, three of which are capable of binding Ca2+. GCAP-1 activates RetGC in low Ca2+ and inhibits it in high Ca2+. In this study we used deletion and substitution analysis to identify regions of GCAP-1 sequence that are specifically required for inhibition and activation. A COOH-terminal sequence within Met157 to Arg182 is required for activation but not for inhibition of RetGC. We localized one essential stretch to 5 residues from Arg178 to Arg182. Another sequence essential for activation is within the N-terminal residues Trp21 to Thr27. The region between EF-hands 1 and 3 of GCAP-1 also contains elements needed for activation of RetGC. Finally, we found that inhibition of RetGC requires the first 9 amino-terminal residues of GCAP-1, but none of the residues from Gln33 to the COOH-terminal Gly205 are specifically required for inhibition. The ability of GCAP-1 mutants to regulate RetGC was tested on total guanylyl cyclase activity present in rod outer segments. In addition, the key mutants were also shown to produce similar effects on recombinant bovine outer segment cyclases GC1 and GC2.
-
Regulation of Photoreceptor Membrane guanylyl cyclases by guanylyl cyclase activator proteins.
Methods (San Diego Calif.), 1999Co-Authors: Alexander M. Dizhoor, James B. HurleyAbstract:Guanylyl cyclase (GC) plays a central role in the responses of vertebrate rod and cone Photoreceptors to light. cGMP is an internal messenger molecule of vertebrate phototransduction. Light stimulates hydrolysis of cGMP, causing the closure of cGMP-dependent cation channels in the plasma Membranes of Photoreceptor outer segments. Light also lowers the concentration of intracellular free Ca(2+) and by doing so it stimulates resynthesis of cGMP by guanylyl cyclase. The guanylyl cyclases that couple Ca(2+) to cGMP synthesis in Photoreceptors are members of a family of transMembrane guanylyl cyclases that includes atrial natriuretic peptide receptors and the heat-stable enterotoxin receptor. The Photoreceptor Membrane guanylyl cyclases, RetGC-1 and RetGC-2 (also referred to as GC-E and GC-F), are regulated intracellularly by two Ca(2+)-binding proteins, GCAP-1 and GCAP-2. GCAPs bind Ca(2+) at three functional EF-hand structures. Several lines of biochemical evidence suggest that guanylyl cyclase activator proteins (GCAPs) bind constitutively to an intracellular domain of RetGCs. In the absence of Ca(2+) GCAP stimulates and in the presence of Ca(2+) it inhibits cyclase activity. Proper functioning of RetGC and GCAP is necessary not only for normal photoresponses but also for Photoreceptor viability since mutations in RetGC and in GCAP cause Photoreceptor degeneration.
-
domain specific stabilization of Photoreceptor Membrane guanylyl cyclase by adenine nucleotides and guanylyl cyclase activating proteins gcaps
Biochemistry, 1997Co-Authors: Chandra L Tucker, Richard P Laura, James B. HurleyAbstract:In Photoreceptor outer segments, particulate guanylyl cyclase (RetGC) is stimulated at low intracellular Ca2+ concentrations by guanylyl cyclase activating protein (GCAP), a Ca2+-sensitive activator, to resynthesize light-depleted cGMP. In washed outer segment Membranes, we find that GCAP-stimulable RetGC is rapidly inactivated at physiological temperatures (30-37 degrees C). Under the same conditions, RetGC remains competent for stimulation by S-100 protein preparations or Mn2+/Triton X-100, indicating that the cyclase catalytic domain remains functional. GCAPs and adenine nucleotides protect against inactivation. Protection by GCAPs is independent of Ca2+ concentration, suggesting that there is a Ca2+-independent interaction between GCAP and RetGC. Protection by ATP (EC50 = 150 microM) is not due to phosphorylation, since the nonhydrolyzable analogue adenylyl imidodiphosphate (AMP-PNP) protects equally well. In addition to their roles in protection, ATP and AMP-PNP also slowly stimulate cyclase activity. In parallel with the functional change in RetGC at physiological temperatures, we also observe a structural change. A 62-kDa intracellular fragment of RetGC-1 becomes more sensitive to cleavage by trypsin after preincubation at 30 degrees C unless ATP, AMP-PNP, or GCAP is present. Adenine nucleotides and GCAPs thus protect RetGC structurally, as well as functionally.
-
cloning sequencing and expression of a 24 kda ca2 binding protein activating Photoreceptor guanylyl cyclase
Journal of Biological Chemistry, 1995Co-Authors: Alexander M. Dizhoor, Elena V Olshevskaya, William J Henzel, Susan C Wong, John T Stults, Irina Ankoudinova, James B. HurleyAbstract:Abstract Two vertebrate Photoreceptor-specific Membrane guanylyl cyclases, RetGC-1 and RetGC-2, are activated by a soluble 24-kDa retinal protein, p24, in a Ca2+-sensitive manner (Dizhoor, A. M., Lowe, D. G., Olshevskaya, E. V., Laura, R. P., and Hurley, J. B.(1994) Neuron 12, 1345-1352; Lowe, D. G., Dizhoor, A. M., Liu, K., Gu, O., Laura, R., Lu, L., and Hurley, J. B.(1995) Proc. Natl. Acad. Sci. U. S. A. 92, 5535-5539). The primary structure of bovine p24 has been derived from peptide sequencing and from its cDNA. p24 is a new EF-hand-type Ca2+-binding protein, related but not identical to another guanylyl cyclase-activating protein, GCAP (Palczewski, K., Subbaraya, I., Gorczyca, W. A., Helekar, B. S., Ruiz, C. C., Ohguro, H. Huang, J., Zhao, X., Crabb, J. W., Johnson, R. S., Walsh, K. A., Gray-Keller, M. P., Detwiler, P. B., and Baehr, W.(1994) Neuron 13, 395-404) and other members of the recoverin family of Ca2+-binding proteins. Antibodies against a truncated fusion protein and against a p24-specific synthetic peptide specifically recognize retinal p24 on immunoblot. Both antibodies inhibit activation of Photoreceptor Membrane guanylyl cyclase by purified p24. p24 is found only in retina, and it copurifies with outer segment Membranes. Immunocytochemical analysis shows that it is present in rod Photoreceptor cells. An immobilized antibody column was used to purify p24 from a heat-treated retinal extract. Purified p24 appears on SDS-polyacrylamide gel electrophoresis as a homogenous protein not contaminated with GCAP, and it activates Photoreceptor guanylyl cyclase in vitro at submicromolar concentrations. Ca2+ inhibits this activation with an EC50 near 200 nM and a Hill coefficient of 1.7. Recombinant p24 expressed in 293 cells effectively stimulates Photoreceptor guanylyl cyclase. These findings demonstrate that p24, like GCAP, imparts Ca2+ sensitivity to Photoreceptor Membrane guanylyl cyclase. We propose that p24 be referred to as GCAP-2 and that GCAP be referred to as GCAP-1.
-
the human Photoreceptor Membrane guanylyl cyclase retgc is present in outer segments and is regulated by calcium and a soluble activator
Neuron, 1994Co-Authors: Alexander M. Dizhoor, James B. Hurley, David G Lowe, Elena V Olshevskaya, Richard P LauraAbstract:A human Photoreceptor Membrane guanylyl cyclase, RetGC, was recently cloned and expressed, but its localization and manner of regulation were not defined. We report here that RetGC is detected primarily in outer segments of human Photoreceptor cells. Recombinant RetGC can be stimulated by a soluble retinal-specific factor. Ca2+ interferes with stimulation of RetGC by this factor with a cooperativity coefficient of 1.7 and EC50 near 200 nM. The Ca2+ sensitivities of recombinant RetGC and of guanylyl cyclase activity from rod outer segment Membranes are very similar. Our findings indicate that RetGC is a Photoreceptor-specific guanylyl cyclase which is stimulated by a retinal-specific activator and inhibited by physiologically relevant concentrations of free Ca2+. The Ca2+ sensitivity of RetGC may be responsible for some of the previously reported effects of Ca2+ on light adaptation and recovery of the dark state.
Alexander M. Dizhoor - One of the best experts on this subject based on the ideXlab platform.
-
a g86r mutation in the calcium sensor protein gcap1 alters regulation of retinal guanylyl cyclase and causes dominant cone rod degeneration
Journal of Biological Chemistry, 2019Co-Authors: Igor V Peshenko, Elena V Olshevskaya, Artur V Cideciyan, Alexander Sumaroka, Alexander Scholten, Seher Abbas, Karlwilhelm Koch, Samuel G Jacobson, Alexander M. DizhoorAbstract:The guanylyl cyclase-activating protein, GCAP1, activates Photoreceptor Membrane guanylyl cyclase (RetGC) in the light, when free Ca2+ concentrations decline, and decelerates the cyclase in the dark, when Ca2+ concentrations rise. Here, we report a novel mutation, G86R, in the GCAP1 (GUCA1A) gene in a family with a dominant retinopathy. The G86R substitution in a "hinge" region connecting EF-hand domains 2 and 3 in GCAP1 strongly interfered with its Ca2+-dependent activator-to-inhibitor conformational transition. The G86R-GCAP1 variant activated RetGC at low Ca2+ concentrations with higher affinity than did the WT GCAP1, but failed to decelerate the cyclase at the Ca2+ concentrations characteristic of dark-adapted Photoreceptors. Ca2+-dependent increase in Trp94 fluorescence, indicative of the GCAP1 transition to its RetGC inhibiting state, was suppressed and shifted to a higher Ca2+ range. Conformational changes in G86R GCAP1 detectable by isothermal titration calorimetry (ITC) also became less sensitive to Ca2+, and the dose dependence of the G86R GCAP1-RetGC1 complex inhibition by retinal degeneration 3 (RD3) protein was shifted toward higher than normal concentrations. Our results indicate that the flexibility of the hinge region between EF-hands 2 and 3 is required for placing GCAP1-regulated Ca2+ sensitivity of the cyclase within the physiological range of intracellular Ca2+ at the expense of reducing GCAP1 affinity for the target enzyme. The disease-linked mutation of the hinge Gly86, leading to abnormally high affinity for the target enzyme and reduced Ca2+ sensitivity of GCAP1, is predicted to abnormally elevate cGMP production and Ca2+ influx in Photoreceptors in the dark.
-
mapping sites in guanylyl cyclase activating protein 1 required for regulation of Photoreceptor Membrane guanylyl cyclases
Journal of Biological Chemistry, 1999Co-Authors: Dmitri M Krylov, Alexander M. Dizhoor, Gregory A Niemi, James B. HurleyAbstract:Guanylyl cyclase activating protein (GCAP)-1 regulates Photoreceptor Membrane guanylyl cyclase, RetGC, in a Ca2+-sensitive manner. It contains four Ca2+-binding motifs, EF-hands, three of which are capable of binding Ca2+. GCAP-1 activates RetGC in low Ca2+ and inhibits it in high Ca2+. In this study we used deletion and substitution analysis to identify regions of GCAP-1 sequence that are specifically required for inhibition and activation. A COOH-terminal sequence within Met157 to Arg182 is required for activation but not for inhibition of RetGC. We localized one essential stretch to 5 residues from Arg178 to Arg182. Another sequence essential for activation is within the N-terminal residues Trp21 to Thr27. The region between EF-hands 1 and 3 of GCAP-1 also contains elements needed for activation of RetGC. Finally, we found that inhibition of RetGC requires the first 9 amino-terminal residues of GCAP-1, but none of the residues from Gln33 to the COOH-terminal Gly205 are specifically required for inhibition. The ability of GCAP-1 mutants to regulate RetGC was tested on total guanylyl cyclase activity present in rod outer segments. In addition, the key mutants were also shown to produce similar effects on recombinant bovine outer segment cyclases GC1 and GC2.
-
Regulation of Photoreceptor Membrane guanylyl cyclases by guanylyl cyclase activator proteins.
Methods (San Diego Calif.), 1999Co-Authors: Alexander M. Dizhoor, James B. HurleyAbstract:Guanylyl cyclase (GC) plays a central role in the responses of vertebrate rod and cone Photoreceptors to light. cGMP is an internal messenger molecule of vertebrate phototransduction. Light stimulates hydrolysis of cGMP, causing the closure of cGMP-dependent cation channels in the plasma Membranes of Photoreceptor outer segments. Light also lowers the concentration of intracellular free Ca(2+) and by doing so it stimulates resynthesis of cGMP by guanylyl cyclase. The guanylyl cyclases that couple Ca(2+) to cGMP synthesis in Photoreceptors are members of a family of transMembrane guanylyl cyclases that includes atrial natriuretic peptide receptors and the heat-stable enterotoxin receptor. The Photoreceptor Membrane guanylyl cyclases, RetGC-1 and RetGC-2 (also referred to as GC-E and GC-F), are regulated intracellularly by two Ca(2+)-binding proteins, GCAP-1 and GCAP-2. GCAPs bind Ca(2+) at three functional EF-hand structures. Several lines of biochemical evidence suggest that guanylyl cyclase activator proteins (GCAPs) bind constitutively to an intracellular domain of RetGCs. In the absence of Ca(2+) GCAP stimulates and in the presence of Ca(2+) it inhibits cyclase activity. Proper functioning of RetGC and GCAP is necessary not only for normal photoresponses but also for Photoreceptor viability since mutations in RetGC and in GCAP cause Photoreceptor degeneration.
-
cloning sequencing and expression of a 24 kda ca2 binding protein activating Photoreceptor guanylyl cyclase
Journal of Biological Chemistry, 1995Co-Authors: Alexander M. Dizhoor, Elena V Olshevskaya, William J Henzel, Susan C Wong, John T Stults, Irina Ankoudinova, James B. HurleyAbstract:Abstract Two vertebrate Photoreceptor-specific Membrane guanylyl cyclases, RetGC-1 and RetGC-2, are activated by a soluble 24-kDa retinal protein, p24, in a Ca2+-sensitive manner (Dizhoor, A. M., Lowe, D. G., Olshevskaya, E. V., Laura, R. P., and Hurley, J. B.(1994) Neuron 12, 1345-1352; Lowe, D. G., Dizhoor, A. M., Liu, K., Gu, O., Laura, R., Lu, L., and Hurley, J. B.(1995) Proc. Natl. Acad. Sci. U. S. A. 92, 5535-5539). The primary structure of bovine p24 has been derived from peptide sequencing and from its cDNA. p24 is a new EF-hand-type Ca2+-binding protein, related but not identical to another guanylyl cyclase-activating protein, GCAP (Palczewski, K., Subbaraya, I., Gorczyca, W. A., Helekar, B. S., Ruiz, C. C., Ohguro, H. Huang, J., Zhao, X., Crabb, J. W., Johnson, R. S., Walsh, K. A., Gray-Keller, M. P., Detwiler, P. B., and Baehr, W.(1994) Neuron 13, 395-404) and other members of the recoverin family of Ca2+-binding proteins. Antibodies against a truncated fusion protein and against a p24-specific synthetic peptide specifically recognize retinal p24 on immunoblot. Both antibodies inhibit activation of Photoreceptor Membrane guanylyl cyclase by purified p24. p24 is found only in retina, and it copurifies with outer segment Membranes. Immunocytochemical analysis shows that it is present in rod Photoreceptor cells. An immobilized antibody column was used to purify p24 from a heat-treated retinal extract. Purified p24 appears on SDS-polyacrylamide gel electrophoresis as a homogenous protein not contaminated with GCAP, and it activates Photoreceptor guanylyl cyclase in vitro at submicromolar concentrations. Ca2+ inhibits this activation with an EC50 near 200 nM and a Hill coefficient of 1.7. Recombinant p24 expressed in 293 cells effectively stimulates Photoreceptor guanylyl cyclase. These findings demonstrate that p24, like GCAP, imparts Ca2+ sensitivity to Photoreceptor Membrane guanylyl cyclase. We propose that p24 be referred to as GCAP-2 and that GCAP be referred to as GCAP-1.
-
the human Photoreceptor Membrane guanylyl cyclase retgc is present in outer segments and is regulated by calcium and a soluble activator
Neuron, 1994Co-Authors: Alexander M. Dizhoor, James B. Hurley, David G Lowe, Elena V Olshevskaya, Richard P LauraAbstract:A human Photoreceptor Membrane guanylyl cyclase, RetGC, was recently cloned and expressed, but its localization and manner of regulation were not defined. We report here that RetGC is detected primarily in outer segments of human Photoreceptor cells. Recombinant RetGC can be stimulated by a soluble retinal-specific factor. Ca2+ interferes with stimulation of RetGC by this factor with a cooperativity coefficient of 1.7 and EC50 near 200 nM. The Ca2+ sensitivities of recombinant RetGC and of guanylyl cyclase activity from rod outer segment Membranes are very similar. Our findings indicate that RetGC is a Photoreceptor-specific guanylyl cyclase which is stimulated by a retinal-specific activator and inhibited by physiologically relevant concentrations of free Ca2+. The Ca2+ sensitivity of RetGC may be responsible for some of the previously reported effects of Ca2+ on light adaptation and recovery of the dark state.
A. V. Belushkin - One of the best experts on this subject based on the ideXlab platform.
-
Small-angle neutron and X-ray scattering analysis of the supramolecular organization of rhodopsin in Photoreceptor Membrane
Biochimica et biophysica acta. Biomembranes, 2019Co-Authors: T. B. Feldman, Oleksandr I. Ivankov, T. N. Murugova, Alexander I. Kuklin, M. A. Yakovleva, Valentin Gordeliy, O. A. Smitienko, Irina B. Kolchugina, Adam Round, A. V. BelushkinAbstract:Abstract The supramolecular organization of the visual pigment rhodopsin in the Photoreceptor Membrane remains contentious. Specifically, whether this G protein-coupled receptor functions as a monomer or dimer remains unknown, as does the presence or absence of ordered packing of rhodopsin molecules in the Photoreceptor Membrane. Completely opposite opinions have been expressed on both issues. Herein, using small-angle neutron and X-ray scattering approaches, we performed a comparative analysis of the structural characteristics of the Photoreceptor Membrane samples in buffer, both in the outer segment of Photoreceptor cells, and in the free Photoreceptor disks. The average distance between the centers of two neighboring rhodopsin molecules was found to be ~5.8 nm in both cases. The results indicate an unusually high packing density of rhodopsin molecules in the Photoreceptor Membrane, but molecules appear to be randomly distributed in the Membrane without any regular ordering.
-
Study of visual pigment rhodopsin supramolecular organization in Photoreceptor Membrane by small-angle neutron scattering method with contrast variation
Doklady. Biochemistry and biophysics, 2015Co-Authors: T. B. Feldman, Oleksandr I. Ivankov, T. N. Murugova, Alexander I. Kuklin, P. V. Shelyakin, M. A. Yakovleva, Valentin Gordeliy, A. V. Belushkin, Mikhail A. OstrovskyAbstract:Supramolecular organization of rhodopsin in the Photoreceptor Membrane was investigated by small-angle neutron scattering method. The experiments, which were performed with mixtures of heavy/light water as solvent (contrast variation method), were aimed at obtaining information about the lipid and protein components of the Photoreceptor disc Membrane separately. It was shown that the packaging density of the rhodopsin molecules in the Photoreceptor Membrane was unusually high: the distance between the centers of the molecules was approximately 56 A. The probability of the monomeric state of rhodopsin molecules in the Photoreceptor Membrane, according to the data obtained, is rather high.
T. B. Feldman - One of the best experts on this subject based on the ideXlab platform.
-
Small-angle neutron and X-ray scattering analysis of the supramolecular organization of rhodopsin in Photoreceptor Membrane
Biochimica et biophysica acta. Biomembranes, 2019Co-Authors: T. B. Feldman, Oleksandr I. Ivankov, T. N. Murugova, Alexander I. Kuklin, M. A. Yakovleva, Valentin Gordeliy, O. A. Smitienko, Irina B. Kolchugina, Adam Round, A. V. BelushkinAbstract:Abstract The supramolecular organization of the visual pigment rhodopsin in the Photoreceptor Membrane remains contentious. Specifically, whether this G protein-coupled receptor functions as a monomer or dimer remains unknown, as does the presence or absence of ordered packing of rhodopsin molecules in the Photoreceptor Membrane. Completely opposite opinions have been expressed on both issues. Herein, using small-angle neutron and X-ray scattering approaches, we performed a comparative analysis of the structural characteristics of the Photoreceptor Membrane samples in buffer, both in the outer segment of Photoreceptor cells, and in the free Photoreceptor disks. The average distance between the centers of two neighboring rhodopsin molecules was found to be ~5.8 nm in both cases. The results indicate an unusually high packing density of rhodopsin molecules in the Photoreceptor Membrane, but molecules appear to be randomly distributed in the Membrane without any regular ordering.
-
Study of visual pigment rhodopsin supramolecular organization in Photoreceptor Membrane by small-angle neutron scattering method with contrast variation
Doklady. Biochemistry and biophysics, 2015Co-Authors: T. B. Feldman, Oleksandr I. Ivankov, T. N. Murugova, Alexander I. Kuklin, P. V. Shelyakin, M. A. Yakovleva, Valentin Gordeliy, A. V. Belushkin, Mikhail A. OstrovskyAbstract:Supramolecular organization of rhodopsin in the Photoreceptor Membrane was investigated by small-angle neutron scattering method. The experiments, which were performed with mixtures of heavy/light water as solvent (contrast variation method), were aimed at obtaining information about the lipid and protein components of the Photoreceptor disc Membrane separately. It was shown that the packaging density of the rhodopsin molecules in the Photoreceptor Membrane was unusually high: the distance between the centers of the molecules was approximately 56 A. The probability of the monomeric state of rhodopsin molecules in the Photoreceptor Membrane, according to the data obtained, is rather high.
-
Spectral characteristics of fluorophores formed via interaction between all-trans-retinal with rhodopsin and lipids in Photoreceptor Membrane of retina rod outer segments
Biochemistry (Moscow) Supplement Series A: Membrane and Cell Biology, 2009Co-Authors: M. Yu. Loguinova, T. B. Feldman, V. E. Zagidullin, Y. V. Rostovtseva, Vladimir Z. Paschenko, Andrei B. Rubin, M. A. OstrovskyAbstract:It is shown that all-trans-retinal under model conditions of its excessive accumulation in Photoreceptor Membranes interacts with amino groups of rhodopsin and lipids, forming at least three distinct fluorophores with fluorescence quantum yield 20–40 times higher than that of free all-trans-retinal. These retinal derivatives are likely precursors of photo- and cytotoxic fluorophores of lipofuscin and in particular of A2E. Spectral characteristics of fluorophores have been described. Picosecond time-resolved laser fluorescence spectroscopy was used to study kinetics of fluorescence decay of both free and bound all-trans-retinal; fluorophores were determined and their lifetimes have been measured. Based on calculations it is shown that the decay kinetics of all-trans-retinal derivatives consists of three components with lifetimes equal to 48, 208, and 900 ps; kinetics of free all-trans-retinal is monoexponential with lifetime of 31 ps. The chemical nature of fluorophores with the lifetimes obtained is discussed.
-
Light damaging action of all-trans-retinal and its derivatives on rhodopsin molecules in the Photoreceptor Membrane
Biochemistry (Moscow), 2008Co-Authors: M. Yu. Loginova, T. B. Feldman, Y. V. Rostovtseva, M. A. OstrovskyAbstract:We have reproduced the model system containing A2-rhodopsin, NR-PE, A2-PE, and ATR-dimer-PE in order to study photosensitized damage of rhodopsin within Photoreceptor Membranes of rod outer segments. We have demonstrated that irradiation of such a system with visible light (400–700 nm) distorts the most important functional property of native visual pigment—its ability to regenerate after addition of 11- cis -retinal in the dark. We have also shown that all- trans -retinal bound to Membrane phospholipids and rhodopsin has less photosensitizing activity that free all- trans -retinal.
Dennis S Rice - One of the best experts on this subject based on the ideXlab platform.
-
adiponectin receptor 1 conserves docosahexaenoic acid and promotes Photoreceptor cell survival
Nature Communications, 2015Co-Authors: Dennis S Rice, Jorgelina M Calandria, William C Gordon, Yongdong Zhou, C M Gelfman, Minghao Jin, Eric J Knott, Bo ChangAbstract:Docosahexaenoic acid is a major and important retinal fatty acid that is recruited and retained in the Photoreceptor Membrane via an unknown mechanism. Here, Rice et al. show that adiponectin receptor 1 is a key molecular switch for docosahexaenoic acid Membrane homeostasis and Photoreceptor cell function.