Positively charged retinoids are potent and selective inhibitors of the trans-cis isomerization in the retinoid (visual) cycle.

Abstract:

:In vertebrate retinal photoreceptors, photoisomerization of opsin-bound visual chromophore 11-cis-retinal to all-trans-retinal triggers phototransduction events. Regeneration of the chromophore is a critical step in restoring photoreceptors to their dark-adapted state. This regeneration process, called the retinoid cycle, takes place in the photoreceptor outer segments and in the retinal pigmented epithelium (RPE). We have suggested that the regeneration of the chromophore might occur through a retinyl carbocation intermediate. Here, we provide evidence that isomerization is inhibited by positively charged retinoids, which could act as transition state analogs of the isomerization process. We demonstrate that retinylamine (Ret-NH2) potently and selectively inhibits the isomerization step of the retinoid cycle in vitro and in vivo. Ret-NH2 binds a protein(s) in the RPE microsomes, but it does not bind RPE65, a protein implicated in the isomerization reaction. Although Ret-NH2 inhibits the regeneration of visual chromophore in rods and, in turn, severely attenuates rod responses, it has a much smaller effect on cone function in mice. Ret-NH2 interacts only at micromolar concentrations with retinoic acid receptor, does not activate retinoid-X receptor, and is not a substrate for CYP26s, the retinoic acid-metabolizing cytochrome P450 enzymes. Ret-NH2 can be a significant investigational tool to study the mechanism of regeneration of visual chromophore.

authors

Golczak M,Kuksa V,Maeda T,Moise AR,Palczewski K

doi

10.1073/pnas.0503318102

keywords:

subject

Has Abstract

pub_date

2005-06-07 00:00:00

pages

8162-7

issue

23

eissn

0027-8424

issn

1091-6490

pii

0503318102

journal_volume

102

pub_type

杂志文章
  • Global gene expression analysis identifies molecular pathways distinguishing blastocyst dormancy and activation.

    abstract::Delayed implantation (embryonic diapause) occurs when the embryo at the blastocyst stage achieves a state of suspended animation. During this period, blastocyst growth is very slow, with minimal or no cell division. Nearly 100 mammals in seven different orders undergo delayed implantation, but the underlying molecular...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0402597101

    authors: Hamatani T,Daikoku T,Wang H,Matsumoto H,Carter MG,Ko MS,Dey SK

    更新日期:2004-07-13 00:00:00

  • Direct gene transfer into human cultured cells facilitated by laser micropuncture of the cell membrane.

    abstract::The selective alteration of the cellular genome by laser microbeam irradiation has been extensively applied in cell biology. We report here the use of the third harmonic (355 nm) of an yttrium-aluminum garnet laser to facilitate the direct transfer of the neo gene into cultured human HT1080-6TG cells. The resultant tr...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.84.12.4180

    authors: Tao W,Wilkinson J,Stanbridge EJ,Berns MW

    更新日期:1987-06-01 00:00:00

  • Extensive and specific responses of a eukaryote to bacterial quorum-sensing signals.

    abstract::Many bacteria use N-acyl homoserine lactone (AHL) signals to coordinate the behavior of individual cells in a local population. The successful infection of eukaryotic hosts by bacteria seems to depend particularly on such AHL-mediated "quorum-sensing" regulation. We have used proteome analysis to show that a eukaryoti...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.262672599

    authors: Mathesius U,Mulders S,Gao M,Teplitski M,Caetano-Anolles G,Rolfe BG,Bauer WD

    更新日期:2003-02-04 00:00:00

  • Ocean acidification causes bleaching and productivity loss in coral reef builders.

    abstract::Ocean acidification represents a key threat to coral reefs by reducing the calcification rate of framework builders. In addition, acidification is likely to affect the relationship between corals and their symbiotic dinoflagellates and the productivity of this association. However, little is known about how acidificat...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0804478105

    authors: Anthony KR,Kline DI,Diaz-Pulido G,Dove S,Hoegh-Guldberg O

    更新日期:2008-11-11 00:00:00

  • Independent role for presynaptic FMRP revealed by an FMR1 missense mutation associated with intellectual disability and seizures.

    abstract::Fragile X syndrome (FXS) results in intellectual disability (ID) most often caused by silencing of the fragile X mental retardation 1 (FMR1) gene. The resulting absence of fragile X mental retardation protein 1 (FMRP) leads to both pre- and postsynaptic defects, yet whether the pre- and postsynaptic functions of FMRP ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1423094112

    authors: Myrick LK,Deng PY,Hashimoto H,Oh YM,Cho Y,Poidevin MJ,Suhl JA,Visootsak J,Cavalli V,Jin P,Cheng X,Warren ST,Klyachko VA

    更新日期:2015-01-27 00:00:00

  • Arabidopsis systemic immunity uses conserved defense signaling pathways and is mediated by jasmonates.

    abstract::In the absence of adaptive immunity displayed by animals, plants respond locally to biotic challenge via inducible basal defense networks activated through recognition and response to conserved pathogen-associated molecular patterns. In addition, immunity can be induced in tissues remote from infection sites by system...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0605423104

    authors: Truman W,Bennett MH,Kubigsteltig I,Turnbull C,Grant M

    更新日期:2007-01-16 00:00:00

  • Attenuation of thermal nociception and hyperalgesia by VR1 blockers.

    abstract::Vanilloid receptor subunit 1 (VR1) appears to play a critical role in the transduction of noxious chemical and thermal stimuli by sensory nerve endings in peripheral tissues. Thus, VR1 antagonists are useful compounds to unravel the contribution of this receptor to pain perception, as well as to induce analgesia. We h...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.022285899

    authors: García-Martinez C,Humet M,Planells-Cases R,Gomis A,Caprini M,Viana F,De La Pena E,Sanchez-Baeza F,Carbonell T,De Felipe C,Pérez-Paya E,Belmonte C,Messeguer A,Ferrer-Montiel A

    更新日期:2002-02-19 00:00:00

  • Differences in spontaneous mutation frequencies as a function of environmental stress in soil fungi at "Evolution Canyon," Israel.

    abstract::When various wild strains of Penicillium lanosum and Aspergillus niger were placed in the same mild laboratory environment, their frequencies of new spontaneous mutations were clearly related to whether they had been isolated from a region of high or low microclimatic stress. In the mild environment, the total frequen...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0801995105

    authors: Lamb BC,Mandaokar S,Bahsoun B,Grishkan I,Nevo E

    更新日期:2008-04-15 00:00:00

  • Structures of the apo- and the metal ion-activated forms of the diphtheria tox repressor from Corynebacterium diphtheriae.

    abstract::The diphtheria tox repressor (DtxR) of Corynebacterium diphtheriae plays a critical role in the regulation of diphtheria toxin expression and the control of other iron-sensitive genes. The crystal structures of apo-DtxR and of the metal ion-activated form of the repressor have been solved and used to identify motifs i...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.92.21.9843

    authors: Schiering N,Tao X,Zeng H,Murphy JR,Petsko GA,Ringe D

    更新日期:1995-10-10 00:00:00

  • Predicting protein function from structure: unique structural features of proteases.

    abstract::We have noted consistent structural similarities among unrelated proteases. In comparison with other proteins of similar size, proteases have smaller than average surface areas, smaller radii of gyration, and higher C(alpha) densities. These findings imply that proteases are, as a group, more tightly packed than other...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.070548997

    authors: Stawiski EW,Baucom AE,Lohr SC,Gregoret LM

    更新日期:2000-04-11 00:00:00

  • Direct three-dimensional visualization of membrane disruption by amyloid fibrils.

    abstract::Protein misfolding and aggregation cause serious degenerative conditions such as Alzheimer's, Parkinson, and prion diseases. Damage to membranes is thought to be one of the mechanisms underlying cellular toxicity of a range of amyloid assemblies. Previous studies have indicated that amyloid fibrils can cause membrane ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1206325109

    authors: Milanesi L,Sheynis T,Xue WF,Orlova EV,Hellewell AL,Jelinek R,Hewitt EW,Radford SE,Saibil HR

    更新日期:2012-12-11 00:00:00

  • Polyglutamine-expanded ataxin-7 inhibits STAGA histone acetyltransferase activity to produce retinal degeneration.

    abstract::Spinocerebellar ataxia type 7 (SCA7) is characterized by cone-rod dystrophy retinal degeneration and is caused by a polyglutamine [poly(Q)] expansion within ataxin-7, a protein of previously unknown function. Here, we report that ataxin-7 is an integral component of the mammalian STAGA (SPT3-TAF9-ADA-GCN5 acetyltransf...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0503505102

    authors: Palhan VB,Chen S,Peng GH,Tjernberg A,Gamper AM,Fan Y,Chait BT,La Spada AR,Roeder RG

    更新日期:2005-06-14 00:00:00

  • Tumor detection and elimination by a targeted gallium corrole.

    abstract::Sulfonated gallium(III) corroles are intensely fluorescent macrocyclic compounds that spontaneously assemble with carrier proteins to undergo cell entry. We report in vivo imaging and therapeutic efficacy of a tumor-targeted corrole noncovalently assembled with a heregulin-modified protein directed at the human epider...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0901531106

    authors: Agadjanian H,Ma J,Rentsendorj A,Valluripalli V,Hwang JY,Mahammed A,Farkas DL,Gray HB,Gross Z,Medina-Kauwe LK

    更新日期:2009-04-14 00:00:00

  • The Arf GTPase-activating protein ASAP1 regulates the actin cytoskeleton.

    abstract::Arf family GTP-binding proteins are best characterized as regulators of membrane traffic, but recent studies indicate an additional role in cytoskeletal organization. An Arf GTPase-activating protein of the centaurin beta family, ASAP1 (also known as centaurin beta4), binds Arf and two other known regulators of the ac...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.070552297

    authors: Randazzo PA,Andrade J,Miura K,Brown MT,Long YQ,Stauffer S,Roller P,Cooper JA

    更新日期:2000-04-11 00:00:00

  • A vertebrate myosin-I structure reveals unique insights into myosin mechanochemical tuning.

    abstract::Myosins are molecular motors that power diverse cellular processes, such as rapid organelle transport, muscle contraction, and tension-sensitive anchoring. The structural adaptations in the motor that allow for this functional diversity are not known, due, in part, to the lack of high-resolution structures of highly t...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1321022111

    authors: Shuman H,Greenberg MJ,Zwolak A,Lin T,Sindelar CV,Dominguez R,Ostap EM

    更新日期:2014-02-11 00:00:00

  • Perinatal antidepressant exposure alters cortical network function in rodents.

    abstract::Serotonin (5-HT) plays a key role in early brain development, and manipulation of 5-HT levels during this period can have lasting neurobiological and behavioral consequences. It is unclear how perinatal exposure to drugs, such as selective serotonin reuptake inhibitors (SSRIs), impacts cortical neural network function...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1109353108

    authors: Simpson KL,Weaver KJ,de Villers-Sidani E,Lu JY,Cai Z,Pang Y,Rodriguez-Porcel F,Paul IA,Merzenich M,Lin RC

    更新日期:2011-11-08 00:00:00

  • Transgenes are dispensable for the RNA degradation step of cosuppression.

    abstract::Cosuppression results in the degradation of RNA from host genes and homologous transgenes after transcription in the nucleus. By using grafting experiments, we have shown previously that a systemic signal mediates the propagation of cosuppression of Nia host genes and 35S-Nia2 transgenes from silenced 35S-Nia2 transge...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.95.16.9675

    authors: Palauqui JC,Vaucheret H

    更新日期:1998-08-04 00:00:00

  • Enzymes processing somatostatin precursors: an Arg-Lys esteropeptidase from the rat brain cortex converting somatostatin-28 into somatostatin-14.

    abstract::The post-translational proteolytic conversion of somatostatin-14 precursors was studied to characterize the enzyme system responsible for the production of the tetradecapeptide either from its 15-kDa precursor protein or from its COOH-terminal fragment, somatostatin-28. A synthetic undecapeptide Pro-Arg-Glu-Arg-Lys-Al...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.81.21.6662

    authors: Gluschankof P,Morel A,Gomez S,Nicolas P,Fahy C,Cohen P

    更新日期:1984-11-01 00:00:00

  • A pair of adjacent glucocorticoid response elements regulate expression of two mouse metallothionein genes.

    abstract::Synthesis of mouse metallothionein (MT)-I and MT-II is transcriptionally induced by the synthetic glucocorticoid, dexamethasone (DEX) or both in vivo as well as in numerous cell lines. However, the location(s) of a glucocorticoid response element (GRE) has not been described. The observation that a marked MT-I gene, a...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.94.19.10045

    authors: Kelly EJ,Sandgren EP,Brinster RL,Palmiter RD

    更新日期:1997-09-16 00:00:00

  • Competition between native topology and nonnative interactions in simple and complex folding kinetics of natural and designed proteins.

    abstract::We compared folding properties of designed protein Top7 and natural protein S6 by using coarse-grained chain models with a mainly native-centric construct that accounted also for nonnative hydrophobic interactions and desolvation barriers. Top7 and S6 have similar secondary structure elements and are approximately equ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0911844107

    authors: Zhang Z,Chan HS

    更新日期:2010-02-16 00:00:00

  • A link between host plant adaptation and pesticide resistance in the polyphagous spider mite Tetranychus urticae.

    abstract::Plants produce a wide range of allelochemicals to defend against herbivore attack, and generalist herbivores have evolved mechanisms to avoid, sequester, or detoxify a broad spectrum of natural defense compounds. Successful arthropod pests have also developed resistance to diverse classes of pesticides and this adapta...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1213214110

    authors: Dermauw W,Wybouw N,Rombauts S,Menten B,Vontas J,Grbic M,Clark RM,Feyereisen R,Van Leeuwen T

    更新日期:2013-01-08 00:00:00

  • Adult fast myosin pattern and Ca2+-induced slow myosin pattern in primary skeletal muscle culture.

    abstract::A primary muscle cell culture derived from newborn rabbit muscle and growing on microcarriers in suspension was established. When cultured for several weeks, the myotubes in this model develop the completely adult pattern of fast myosin light and heavy chains. When Ca2+ ionophore is added to the culture medium on day ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.94.8.4205

    authors: Kubis HP,Haller EA,Wetzel P,Gros G

    更新日期:1997-04-15 00:00:00

  • Clostridioides difficile infection damages colonic stem cells via TcdB, impairing epithelial repair and recovery from disease.

    abstract::Gastrointestinal infections often induce epithelial damage that must be repaired for optimal gut function. While intestinal stem cells are critical for this regeneration process [R. C. van der Wath, B. S. Gardiner, A. W. Burgess, D. W. Smith, PLoS One 8, e73204 (2013); S. Kozar et al., Cell Stem Cell 13, 626-633 (2013...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1915255117

    authors: Mileto SJ,Jardé T,Childress KO,Jensen JL,Rogers AP,Kerr G,Hutton ML,Sheedlo MJ,Bloch SC,Shupe JA,Horvay K,Flores T,Engel R,Wilkins S,McMurrick PJ,Lacy DB,Abud HE,Lyras D

    更新日期:2020-04-07 00:00:00

  • Associative memory Hamiltonians for structure prediction without homology: alpha/beta proteins.

    abstract::We describe a method for predicting the structure of alpha beta class proteins in the absence of information from homologous structures. The method is based on an associative memory model for short to intermediate range in sequence contacts and a contact potential for long range in sequence contacts. The coefficients ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.252753899

    authors: Hardin C,Eastwood MP,Prentiss MC,Luthey-Schulten Z,Wolynes PG

    更新日期:2003-02-18 00:00:00

  • Variation in virulence among clades of Escherichia coli O157:H7 associated with disease outbreaks.

    abstract::Escherichia coli O157:H7, a toxin-producing food and waterborne bacterial pathogen, has been linked to large outbreaks of gastrointestinal illness for more than two decades. E. coli O157 causes a wide range of clinical illness that varies by outbreak, although factors that contribute to variation in disease severity a...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0710834105

    authors: Manning SD,Motiwala AS,Springman AC,Qi W,Lacher DW,Ouellette LM,Mladonicky JM,Somsel P,Rudrik JT,Dietrich SE,Zhang W,Swaminathan B,Alland D,Whittam TS

    更新日期:2008-03-25 00:00:00

  • Association by hydrogen bonding of mononucleotides in aqueous solution.

    abstract::Evidence for hydrogen bonding between 5'-ribonucleotides in water has been obtained from a 220-MHz proton magnetic resonance study of nitrogenous protons. The amino groups of GMP, AMP, and CMP exhibit proton resonance lines which are somewhat broadened by proton exchange with the solvent at 0 degrees ; their downfield...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.69.8.2025

    authors: Raszka M,Kaplan NO

    更新日期:1972-08-01 00:00:00

  • Uncoupling of growth plate maturation and bone formation in mice lacking both Schnurri-2 and Schnurri-3.

    abstract::Formation and remodeling of the skeleton relies on precise temporal and spatial regulation of genes expressed in cartilage and bone cells. Debilitating diseases of the skeletal system occur when mutations arise that disrupt these intricate genetic regulatory programs. Here, we report that mice bearing parallel null mu...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1003727107

    authors: Jones DC,Schweitzer MN,Wein M,Sigrist K,Takagi T,Ishii S,Glimcher LH

    更新日期:2010-05-04 00:00:00

  • Chronic sleep curtailment, even without extended (>16-h) wakefulness, degrades human vigilance performance.

    abstract::Millions of individuals routinely remain awake for more than 18 h daily, which causes performance decrements. It is unknown if these functional impairments are the result of that extended wakefulness or from the associated shortened sleep durations. We therefore examined changes in objective reaction time performance ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1706694115

    authors: McHill AW,Hull JT,Wang W,Czeisler CA,Klerman EB

    更新日期:2018-06-05 00:00:00

  • Interferon induction of IFITM proteins promotes infection by human coronavirus OC43.

    abstract::IFNs are a family of cytokines that are essential for the antiviral response in vertebrates. Not surprisingly, viruses have adapted to encode virulence factors to cope with the IFN response. Intriguingly, we show here that all three types of interferons, IFN-α, IFN-γ, and IFN-λ, efficiently promote infection by a huma...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1320856111

    authors: Zhao X,Guo F,Liu F,Cuconati A,Chang J,Block TM,Guo JT

    更新日期:2014-05-06 00:00:00

  • Ubiquitin degradation with its substrate, or as a monomer in a ubiquitination-independent mode, provides clues to proteasome regulation.

    abstract::The mechanisms that regulate the ubiquitin (Ub)-proteasome system's own components, although critically important, are largely unknown. Ub, a principal component of the system, must be maintained at adequate levels to support cellular homeostasis under basal and stressed conditions. It was suggested that Ub is degrade...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0905746106

    authors: Shabek N,Herman-Bachinsky Y,Ciechanover A

    更新日期:2009-07-21 00:00:00