Genetic dissection of cyclophilin function. Saturation mutagenesis of the Drosophila cyclophilin homolog ninaA.

Cyclophilins, the intracellular receptors for the widely used immunosuppressant cyclosporin A have been found to be peptidyl-prolyl cis/trans isomerases and have been implicated in intracellular protein folding and trafficking. The Drosophila ninaA gene encodes a photoreceptor-specific cyclophilin homolog involved in rhodopsin biogenesis. ninaA mutants have a 90% reduction in the levels of Rh1 rhodopsin. To gain insight into the role of cyclophilins in vivo, we carried out a genetic screen designed to identify functionally important regions in the ninaA protein. Over 700,000 mutagenized flies were screened for a visible ninaA phenotype and 70 independent mutations in ninaA were isolated and characterized. These mutations provide a detailed dissection of the structure/function relationships in cyclophilin. We also show that mammalian cyclophilins engineered to contain missense mutations found in two temperature-sensitive ninaA alleles display temperature-sensitive prolyl cis/trans isomerase activity.

• Publication year

  1992

• Venue

  Journal of Biological Chemistry

• Publication date

  1992-08-15

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1016/S0021-9258(18)42025-XPMID 1644830
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• s-cyclophilin is retained intracellularly via a unique COOH-terminal sequence and colocalizes with the calcium storage protein calreticulin

  1992cited by this paper
• Protein folding in the cell

  1992cited by this paper
• Rhodopsin, photoreceptor of the rod cell. An emerging pattern for structure and function.

  1992cited by this paper
• Nuclear association of a T-cell transcription factor blocked by FK-506 and cyclosporin A

  1991cited by this paper
• Signal transduction in the visual system of Drosophila.

  1991cited by this paper
• Cyclosporin A inhibits an initial step in folding of transferrin within the endoplasmic reticulum.

  1991cited by this paper
• Two cytoplasmic candidates for immunophilin action are revealed by affinity for a new cyclophilin: one in the presence and one in the absence of CsA.

  1991cited by this paper
• Structure of human cyclophilin and its binding site for cyclosporin A determined by X-ray crystallography and NMR spectroscopy

  1991cited by this paper
• Chemistry and biology of the immunophilins and their immunosuppressive ligands.

  1991cited by this paper
• When worlds collide: immunosuppressants meet protein phosphatases.

  1991cited by this paper
• The cyclophilin homolog ninaA is a tissue-specific integral membrane protein required for the proper synthesis of a subset of Drosophila rhodopsins.

  1991cited by this paper
• Is cyclophilin involved in the immunosuppressive and nephrotoxic mechanism of action of cyclosporin A?

  1991cited by this paper
• Human cyclophilin B: a second cyclophilin gene encodes a peptidyl-prolyl isomerase with a signal sequence.

  1991cited by this paper
• Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes.

  1991cited by this paper
• The cyclophilin multigene family of peptidyl-prolyl isomerases. Characterization of three separate human isoforms.

  1991cited by this paper
• 1H,13C and 15N backbone assignments of cyclophilin when bound to cyclosporin A (CsA) and preliminary structural characterization of the CsA binding site

  1991cited by this paper
• Crystal structure of recombinant human T-cell cyclophilin A at 2.5 A resolution.

  1991cited by this paper
• Cyclosporin A slows collagen triple-helix formation in vivo: indirect evidence for a physiologic role of peptidyl-prolyl cis-trans-isomerase.

  1991cited by this paper
• The cyclophilin homolog ninaA is required in the secretory pathway.

  1991cited by this paper
• Cloning, expression, and purification of human cyclophilin in Escherichia coli and assessment of the catalytic role of cysteines by site-directed mutagenesis.

  1990cited by this paper
• Cyclosporin A: new insights for cell biologists and biochemists.

  1990cited by this paper
• Peptidyl-prolyl cis-trans isomerases, cyclophilin, FK506-binding protein, and ninaA: four of a kind.

  1990cited by this paper
• Folding of ribonuclease T1. 1. Existence of multiple unfolded states created by proline isomerization.

  1990cited by this paper
• Nucleotide sequence of the gene coding for cyclophilin/peptidyl-prolyl cis-trans isomerase of Neurospora crassa

  1990cited by this paper
• A second cyclophilin-related gene in Saccharomyces cerevisiae.

  1990cited by this paper
• Sensitivity to cyclosporin A is mediated by cyclophilin in Neurospora crassa and Saccharomyces cerevisiae

  1989cited by this paper
• Thermal stability and folding of type IV procollagen and effect of peptidyl-prolyl cis-trans-isomerase on the folding of the triple helix.

  1989cited by this paper
• Cyclophilin and peptidyl-prolyl cis-trans isomerase are probably identical proteins

  1989cited by this paper
• Drosophila ninaA gene encodes an eye-specific cyclophilin (cyclosporine A binding protein).

  1989cited by this paper
• The ninaA gene required for visual transduction in Drosophila encodes a homologue of cyclosporin A-binding protein

  1989cited by this paper
• Yeast cyclophilin: isolation and characterization of the protein, cDNA and gene.

  1989cited by this paper
• Peptidyl-prolyl cis-trans isomerase is the cyclosporin A-binding protein cyclophilin

  1989cited by this paper
• Cyclosporin A specifically inhibits function of nuclear proteins involved in T cell activation.

  1989cited by this paper
• Protein-disulphide isomerase and prolyl isomerase act differently and independently as catalysts of protein folding

  1988cited by this paper
• pl Bl5: A cDNA Clone of the Rat mRNA Encoding Cyclophilin

  1988cited by this paper
• Complementary DNA for human T‐cell cyclophilin.

  1987cited by this paper
• Cyclophilin binds to the region of cyclosporine involved in its immunosuppressive activity

  1987cited by this paper
• Catalysis of protein folding by prolyl isomerase

  1987cited by this paper
• The influence of peptidyl-prolyl cis-trans isomerase on the in vitro folding of type III collagen.

  1987cited by this paper
• Ribbon models of macromolecules

  1987cited by this paper
• Use of bacteriophage T7 RNA polymerase to direct selective high-level expression of cloned genes.

  1986cited by this paper
• Enzymatic amplification of beta-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia.

  1985cited by this paper
• Cyclophilin: a specific cytosolic binding protein for cyclosporin A.

  1984cited by this paper
• [Determination of enzymatic catalysis for the cis-trans-isomerization of peptide binding in proline-containing peptides].

  1984cited by this paper
• Isomerization of proline-93 during the unfolding and refolding of ribonuclease A.

  1983cited by this paper
• Mutation that selectively affects rhodopsin concentration in the peripheral photoreceptors of Drosophila melanogaster

  1981cited by this paper
• Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications.

  1979cited by this paper
• DNA sequencing with chain-terminating inhibitors.

  1977cited by this paper
• A note on grammars with regular restrictions

  1973cited by this paper
• [Pseudopupil phenomena in the compound eye of drosophila].

  1971cited by this paper
• Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4

  1970cited by this paper

• Correction: The Retromer Complex Is Required for Rhodopsin Recycling and Its Loss Leads to Photoreceptor Degeneration

  2015cites this paper
• The Retromer Complex Is Required for Rhodopsin Recycling and Its Loss Leads to Photoreceptor Degeneration

  2014cites this paper
• Differential Loss of Prolyl Isomerase or Chaperone Activity of Ran-binding Protein 2 (Ranbp2) Unveils Distinct Physiological Roles of Its Cyclophilin Domain in Proteostasis*

  2014influential citation
• Rhodopsin homeostasis and retinal degeneration: lessons from the fly.

  2013cites this paper
• Xbp1-independent Ire1 signaling is required for photoreceptor differentiation and rhabdomere morphogenesis in Drosophila.

  2013cites this paper
• Degenerative Diseases of the Retina

  2012cites this paper
• From Drosophila to Humans: Reflections on the Roles of the Prolyl Isomerases and Chaperones, Cyclophilins, in Cell Function and Disease

  2012influential citation
• Retinal degeneration in the fly.

  2012cites this paper
• ER stress inhibits neuronal death by promoting autophagy

  2012cites this paper
• ER stress protects from retinal degeneration

  2009cites this paper
• Proteomic analysis of Trypanosoma cruzi resistance to Benznidazole.

  2008cites this paper
• Phototransduction and retinal degeneration in Drosophila

  2007cites this paper
• Regulation of CD147 Cell Surface Expression

  2005cites this paper
• Cell Surface Expression of CD147/EMMPRIN Is Regulated by Cyclophilin 60*

  2005cites this paper
• A cyclophilin from Griffithsia japonica has thermoprotective activity and is affected by CsA.

  2005cites this paper
• Enzymes of Sphingolipid metabolism in Drosophila melanogaster

  2004cites this paper
• Comprehensive Analysis of the Secreted Proteins of the Parasite Haemonchus contortus Reveals Extensive Sequence Variation and Differential Immune Recognition*

  2003cites this paper
• Production and purification of recombinant membrane proteins

  2003cites this paper
• Immunofluorescent studies of the INAD signaling complex and the TRPL ion channel in fly photoreceptors (Drosophila melanogaster and Calliphora vicina) [online]

  2002cites this paper
• FK506 binding protein from a thermophilic archaeon, Methanococcus thermolithotrophicus, has chaperone-like activity in vitro.

  2000cites this paper
• Chapter 9 Genetic dissection of Drosophila phototransduction

  2000cites this paper
• Immunophilins: The next generation

  2000cites this paper
• Chapter 7 Invertebrate visual pigments

  2000cites this paper
• Biochemical and Structural Characterization of a Divergent Loop Cyclophilin from Caenorhabditis elegans *

  1999cites this paper
• Variations of sequences and amino acid compositions of proteins that sustain their biological functions: An analysis of the cyclophilin family of proteins.

  1999cites this paper
• A role for the light-dependent phosphorylation of visual arrestin.

  1999cites this paper
• A genetic method for generating Drosophila eyes composed exclusively of mitotic clones of a single genotype.

  1999cites this paper
• The Peptidyl-prolyl Isomerase Domain of the CyP-40 Cyclophilin Homolog Cpr7 Is Not Required to Support Growth or Glucocorticoid Receptor Activity in Saccharomyces cerevisiae*

  1998cites this paper
• Immunophilins: beyond immunosuppression.

  1998cites this paper
• Biochemical and Genetic Characterization of an FK506-Sensitive Peptidyl Prolyl cis-trans Isomerase from a Thermophilic Archaeon, Methanococcus thermolithotrophicus

  1998cites this paper
• Engineering the folding pathway of insect cells: generation of a stably transformed insect cell line showing improved folding of a recombinant membrane protein.

  1997cites this paper
• Molecular recognition in the HIV-1 capsid/cyclophilin A complex.

  1997cites this paper
• Genetic and biochemical characterization of Drosophila singed, a homolog of the actin bundling protein fascin

  1996cites this paper
• Cyclophilin A is required for an early step in the life cycle of human immunodeficiency virus type 1 before the initiation of reverse transcription

  1996cites this paper
• Cellular functions of immunophilins.

  1996cites this paper
• A multicopy suppressor of a cell cycle defect in S. pombe encodes a heat shock‐inducible 40 kDa cyclophilin‐like protein.

  1996cites this paper
• Biosynthesis and mechanism of action of cyclosporins.

  1996cites this paper
• Structure-function relationships in the FK506-binding protein (FKBP) family of peptidylprolyl cis-trans isomerases.

  1996cites this paper
• Single amino acid mutations in Drosophila fascin disrupt actin bundling function in vivo.

  1996cites this paper
• Isolation of 88F actin mutants of Drosophila melanogaster and possible alterations in the mutant actin structures.

  1996cites this paper
• Defective intracellular transport is the molecular basis of rhodopsin-dependent dominant retinal degeneration.

  1995cites this paper
• Cyclophilin 20 is involved in mitochondrial protein folding in cooperation with molecular chaperones Hsp70 and Hsp60

  1995cites this paper
• Kinetic analysis of cyclophilin-catalyzed prolyl cis/trans isomerization by dynamic NMR spectroscopy.

  1995cites this paper
• Retina-specifically Expressed Novel Subtypes of Bovine Cyclophilin (*)

  1995cites this paper
• Characterization of a cDNA encoding a cytosolic peptidylprolyl cis-trans-isomerase from Blattella germanica.

  1995cites this paper
• Characterization of Vertebrate Homologs of Drosophila Photoreceptor Proteins

  1995cites this paper
• A new family of peptidyl-prolyl isomerases.

  1995cites this paper
• Inhibition of peptidyl-prolyl cis/trans isomerase activity by substrate analog structures: thioxo tetrapeptide-4-nitroanilides.

  1995cites this paper
• Molecular chaperones and intracellular protein translocation.

  1995cites this paper
• Peptidylproline cis/trans isomerases.

  1995cites this paper
• Mutations That Perturb Cyclophilin A Ligand Binding Pocket Confer Cyclosporin A Resistance in Saccharomycescerevisiae(*)

  1995cites this paper
• A Kinetic Analysis of the Folding of Human Carbonic Anhydrase II and Its Catalysis by Cyclophilin (*)

  1995cites this paper
• Über Peptidyl‐Prolyl‐cis/trans‐Isomerasen und ihre Effektoren

  1994cites this paper
• Three-dimensional solution structure of Escherichia coli periplasmic cyclophilin.

  1994cites this paper
• Cloning and characterization of ppiB, a Bacillus subtilis gene which encodes a cyclosporine A‐sensitive peptidyl‐prolyl cis‐trans isomerase

  1994cites this paper
• Thermodynamics of cyclophilin catalyzed peptidyl‐prolyl isomerization by nmr spectroscopy

  1994cites this paper
• A novel peptidyl‐prolyl cisltrans isomerase from Escherichia coli

  1994cites this paper
• Cyclosporin A, FK506, and rapamycin: binding to immunophilins and biological action.

  1994cites this paper
• The cyclophilin homolog NinaA functions as a chaperone, forming a stable complex in vivo with its protein target rhodopsin.

  1994cites this paper
• Mechanism of arrestin 2 function in rhabdomeric photoreceptors.

  1994cites this paper
• Immunophilins in protein folding and immunosuppression 1

  1994cites this paper
• Enzymkatalyse bei Konformerenumwandlungen

  1994cites this paper
• Yeast as model T cells

  1994cites this paper
• Genetic and molecular analysis of the wis2+ gene in fission yeast

  1994cites this paper
• Opsin maturation and targeting to rhabdomeral photoreceptor membranes requires the retinal chromophore.

  1994cites this paper
• Mapping of residues forming the voltage sensor of the voltage-dependent anion-selective channel.

  1993cites this paper
• Immunophilins: structure—function relationship and possible role in microbial pathogenicity

  1993cites this paper
• FK506Inhibits AminoAcidImport inSaccharomyces cerevisiae

  1993cites this paper
• Mechanisms and genetics of photoreceptors desensitization in Drosophila flies.

  1993cites this paper
• Cloning and characterization of cyclophilin C-associated protein: a candidate natural cellular ligand for cyclophilin C.

  1993cites this paper
• Arrestin function in inactivation of G protein-coupled receptor rhodopsin in vivo.

  1993cites this paper
• The FKB2 gene of Saccharomyces cerevisiae, encoding the immunosuppressant-binding protein FKBP-13, is regulated in response to accumulation of unfolded proteins in the endoplasmic reticulum.

  1993cites this paper
• Secondary structure and backbone resonance assignments of the periplasmic cyclophilin type peptidyl-prolyl isomerase from Escherichia coli.

  1993cites this paper
• Proline Isomerases in Microorganisms and Small Eukaryotes a

  1993cites this paper
• Specific cross-linking of the proline isomerase cyclophilin to a non-proline-containing peptide.

  1993cites this paper
• The immunosuppressant FK506 inhibits amino acid import in Saccharomyces cerevisiae

  1993cites this paper
• Structural and evolutionary relationships among the immunophilins: two ubiquitous families of peptidyl‐prolyl cis‐trans isomerases

  1992influential citation
• Phototransduction in Drosophila: a paradigm for the genetic dissection of sensory transduction cascades.

  1992cites this paper