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Etude de l'expression des régulateurs endocytaires, Rab5a et Rab7, dans les adénomes thyroïdiens autonomes

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Les petites protéines GTPases Rab5a et Rab7 sont des régulateurs agissant en tandem de l’endocytose, et de la dégradation de la thyroglobuline iodée. Nous avons étudié l’expression du gène codant l’isoforme Rab5a et Rab7 dans le tissu de quatre nodules autonomes ou chauds, caractérisés par une hyperfixation de l’iode et une synthèse accrue des hormones thyroïdiennes, et dans le tissu périnodulaire mais au repos correspondant. L’étude a également examiné un nodule froid dépourvu d’activité sécrétoire et son tissu périnodulaire normal.
après mise au point de la technique de PCR en temps-réel pur la quantification de l’ADNc de Rab5a et de Rab7, nous concluons que dans le tissu autonome, l’augmentation de l’expression des protéines Rab5a et Rab7 est dû à une régulation positive au niveau de l’expression de l’ARN messager, résultat probable de la stimulation constitutive de ce tissu par le TSH. Par contre, dans le nodule froid, l’expression des protéines ainsi que de l’ARNm de Rab5a et Rab7 ne semble pas varier.
La deuxième partie de ce travail a porté sur l’étude d’un autre régulateur possible de la dégradation de la thyroglobuline iodée dans les lysosomes, la cathepsine D.
Les résultats en « western blot » montrent qu’il y a une augmentation significative aussi bien de l’expression de la forme mature de la protéine que de l’activité enzymatique de cet enzyme dans le tissu hyperactif comparé au tissu mis au repos. La comparaison des résultats obtenues par ces deux méthodes d’investigation montre que dans le nodule autonome, la contenu en protéine est plus important que ne l’est l’activité enzymatique. Après fractionnement subcellulaire, suivi d’une équilibration isopycnique de la fraction MLP en gradient de Percoll®, nous observons que dans les fractions de densités correspondant aux endosomes tardifs, se trouvent une forme mature de la cathepsine D ne possédant pas d’activité. Ce résultat indique la présence dans le tissu hyperfonctionnel d’une maturation prématurée de l’enzyme au niveau d’une compartiment vésiculaire dont le pH serait insuffisant pour révéler l’activité enzymatique.
l’analyse des fractionnements de sept paires de tissus nodulaire et périnodulaire, montre une relocalisation de l’enzyme de la fraction soluble (S) vers la fraction particulaire (MLP). L’enzyme est donc transporté vers le compartiment où son rôle est le plus efficace. Enfin, il existe une corrélation positive entre l’endocytose apicale de la thyroglobuline, et le contenu de la glande en cathepsine D active.

Regulators and effectors of small GTPases : Rho family
Authors: --- ---
ISSN: 00766879 ISBN: 0121828115 9780121828110 9786611050368 1281050369 0080479391 Year: 2006 Volume: 406 Publisher: Amsterdam ; Boston : Elsevier : Academic Press,

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The Ras superfamily (>150 human members) encompasses Ras GTPases involved in cell proliferation, Rho GTPases involved in regulating the cytoskeleton, Rab GTPases involved in membrane targeting/fusion and a group of GTPases including Sar1, Arf, Arl and dynamin involved in vesicle budding/fission. These GTPases act as molecular switches and their activities are controlled by a large number of regulatory molecules that affect either GTP loading (guanine nucleotide exchange factors or GEFs) or GTP hydrolysis (GTPase activating proteins or GAPs). In their active state, they interact with a continua

The G-protein linked receptor : factsbook
Authors: ---
ISBN: 0127384405 9780127384405 Year: 1994 Publisher: London Academic Press

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Catalogues major facts about receptors, G-proteins and effector molecules. Each entry has a common format, using a minimum amount of text, and contains information on the sequence, gene structure, distribution, agonists/antagonists and physiochemical properties of these proteins.

Regulators and effectors of small GTPases.
Authors: --- ---
ISSN: 00766879 ISBN: 0121822346 9786611020842 1281020842 0080522564 0121822265 0121822338 0121822303 9786611011093 1281011096 0080496806 9786611020835 1281020834 0080522556 9786611011130 1281011134 0080496849 9780121822309 9780121822330 9780121822347 9780121822262 Year: 2001 Volume: 325-329-332-333 Publisher: San Diego : Academic Press,

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The critically acclaimed laboratory standard for more than 40 years, Methods in Enzymology is one of the most highly respected publications in the field of biochemistry. Since 1955, each volume has been eagerly awaited, frequently consulted, and praised by researchers and reviewers alike. Now with more than 300 volumes (all of them still in print), the series contains much material still relevant today-truly an essential publication for researchers in all fields of life sciences.This volume and its companions (Volumes 255, 256, 257, and the forthcoming 325, 329,

Keywords

Guanosine triphosphatase. --- ras Proteins. --- ras Proteins --- Monomeric GTP-Binding Proteins --- GTP-Binding Proteins --- Intracellular Signaling Peptides and Proteins --- Peptides --- Carrier Proteins --- GTP Phosphohydrolases --- Proteins --- Amino Acids, Peptides, and Proteins --- Acid Anhydride Hydrolases --- Chemicals and Drugs --- Hydrolases --- Enzymes --- Enzymes and Coenzymes --- Ras proteins. --- G proteins. --- GTP-binding proteins --- GTP regulatory proteins --- Guanine nucleotide-binding proteins --- Guanine nucleotide regulatory proteins --- Guanosine triphosphatase --- Guanosine-trifosfatase --- Guanosinetriphosphatase --- Trifosfatase [Guanosine-] --- Triphosphatase [Guanosine] --- rho GTP-Binding Proteins --- Binding Protein --- Binding Proteins --- Transport Proteins --- Protein, Binding --- Proteins, Binding --- Proteins, Carrier --- Proteins, Transport --- G-Protein --- GTP-Binding Protein --- GTP-Regulatory Protein --- Guanine Nucleotide Coupling Protein --- G-Proteins --- GTP-Regulatory Proteins --- Guanine Nucleotide Regulatory Proteins --- G Protein --- G Proteins --- GTP Binding Protein --- GTP Binding Proteins --- GTP Regulatory Protein --- GTP Regulatory Proteins --- Protein, GTP-Binding --- Protein, GTP-Regulatory --- Proteins, GTP-Binding --- Proteins, GTP-Regulatory --- Intracellular Signaling Peptides --- Intracellular Signaling Proteins --- Peptides, Intracellular Signaling --- Proteins, Intracellular Signaling --- Signaling Peptides, Intracellular --- Signaling Proteins, Intracellular --- P21 (rho)Protein --- rho GTP-Binding Protein --- rho Protein P21 --- rho G-Proteins --- rho GTPases --- rho Small GTP-Binding Proteins --- G-Proteins, rho --- GTP-Binding Protein, rho --- GTP-Binding Proteins, rho --- GTPases, rho --- P21, rho Protein --- rho G Proteins --- rho GTP Binding Protein --- rho GTP Binding Proteins --- rho Small GTP Binding Proteins --- GTP Phosphohydrolase --- GTPase --- GTPases --- Guanosine Triphosphate Phosphohydrolases --- Guanosinetriphosphatases --- Phosphohydrolase, GTP --- Phosphohydrolases, GTP --- Phosphohydrolases, Guanosine Triphosphate --- Triphosphate Phosphohydrolases, Guanosine --- ras-Related G-Proteins --- ras-Related GTP-Binding Proteins --- G-Proteins, Monomeric --- GTP-Binding Proteins, Monomeric --- Monomeric G-Proteins --- Small G-Proteins --- Small GTPases --- ras-Related GTPases --- G Proteins, Monomeric --- G-Proteins, Small --- G-Proteins, ras-Related --- GTP Binding Proteins, Monomeric --- GTP-Binding Proteins, ras-Related --- GTPases, Small --- GTPases, ras-Related --- Monomeric G Proteins --- Monomeric GTP Binding Proteins --- Proteins, ras-Related GTP-Binding --- Small G Proteins --- ras Related G Proteins --- ras Related GTP Binding Proteins --- ras Related GTPases --- Anhydride Hydrolases, Acid --- Hydrolases, Acid Anhydride --- Biochemistry -- Periodicals. --- Biochemistry -- Technique. --- Enzymes -- Collections. --- Enzymes -- Periodicals. --- Enzymologie -- Technique -- Collections. --- GTP Phosphohydrolases. --- GTP phosphohydrolase --- Guanosine triphosphate phosphohydrolase --- GTP phosphohydrolases. --- Cytoplasmic Vesicles --- Physiological effect --- G proteins --- Membrane proteins --- Phosphatases --- Coenzymes and Enzymes --- Biocatalysts --- Molecular Mechanisms of Pharmacological Action --- Protein Binding --- Receptors, Transferrin --- Gene Products, Protein --- Gene Proteins --- Protein Gene Products --- Proteins, Gene --- Polypeptides --- Biocatalyst --- Enzyme --- Carrier Protein --- Transport Protein --- Protein, Carrier --- Protein, Transport --- Protein --- Peptide --- Polypeptide --- Hydrolase --- Small GTPase --- GTPase, Small --- rho GTPase --- GTPase, rho --- Gene expression. --- Gtp phosphohydrolases --- Map kinase signaling system --- Adp-ribosylation factors --- Gtp-binding proteins --- Gtp phosphohydrolase activators --- Gtp-binding protein regulators

Receptors
Authors: ---
ISBN: 1281011215 9786611011215 008049692X 0121822451 9780121822446 9780121822453 0121822443 9780121822460 012182246X Year: 2002 Publisher: San Diego ; London : Academic Press,

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This volume covers topics such as the structure and identification of functional domains of G proteins, and activation of G proteins by receptors or other regulators. The text takes an integrated approach to studying common experimental questions at many different levels related to G proteins. Methods related to G proteins using molecular modeling, systems biology, protein engineering, protein biochemistry, cell biology, and physiology are all accessible in the same volume. The critically acclaimed laboratory standard for more than forty years, Methods in Enzymology is one of the mo

Signal Transduction Protocols
Authors: ---
ISBN: 1588292452 1592598161 9786610359899 1280359897 9781592598168 9781588292452 Year: 2004 Volume: 284 Publisher: Totowa, NJ : Humana Press : Imprint: Humana,

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Carrying on the high standards of the much-acclaimed first edition, highly experienced investigators have extensively updated Signal Transduction Protocols with many of the new approaches that have been transforming the field. Included in this new edition are readily reproducible immunoassays, fluorescence-based assays, high-throughput methods, protein modification assays, lipid second messenger assays, and chromatin immunoprecipitation techniques. Wherever possible, protocols for the assay of general classes of signal transduction components have been identified so they can be adapted to the assay of any member of that class. The protocols follow the successful Methods in Molecular Biology™ series format, each one offering step-by-step laboratory instructions, an introduction outlining the principle behind the technique, lists of the necessary equipment and reagents, and tips on troubleshooting and avoiding known pitfalls. State-of-the-art and eminently practical, Signal Transduction Protocols, 2nd ed. offers novice and experienced researchers alike an indispensable set of standardized, but readily adaptable, approaches for the assay of key signaling molecules-an invaluable tool for all laboratories newly entering the field, expanding the breadth of previous investigations, or seeking to improve an existing approach.

Small GTPases and their regulators. Part B : Rho family
Authors: --- ---
ISBN: 0121821560 0121821579 0121821587 9780121821562 9780121821586 9780121821579 Year: 1995 Volume: 255-256-257 Publisher: New York, NY : Academic Press,

G proteins and signal transduction
Authors: --- ---
ISBN: 0874700469 9780874700466 Year: 1990 Volume: 45 Publisher: New York, N.Y. Rockefeller University Press

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Keywords

G proteins --- Glycogen Storage Disease Type I. --- -G proteins --- -577.32 --- GTP-binding proteins --- GTP regulatory proteins --- Guanine nucleotide-binding proteins --- Guanine nucleotide regulatory proteins --- Membrane proteins --- Information theory in biology --- Deficiency, Glucosephosphatase --- Gierke Disease --- Gierke's Disease --- Glycogen Storage Disease 1 (GSD I) --- von Gierke's Disease --- Glucose-6-Phosphatase Deficiency --- Glucosephosphatase Deficiency --- Glycogenosis 1 --- Hepatorenal Glycogen Storage Disease --- von Gierke Disease --- Deficiencies, Glucose-6-Phosphatase --- Deficiencies, Glucosephosphatase --- Deficiency, Glucose-6-Phosphatase --- Disease, Gierke --- Disease, Gierke's --- Disease, von Gierke --- Disease, von Gierke's --- Gierkes Disease --- Glucose 6 Phosphatase Deficiency --- Glucose-6-Phosphatase Deficiencies --- Glucosephosphatase Deficiencies --- von Gierkes Disease --- Glucose-6-Phosphatase --- deficiency --- Cellular signal transduction --- Glycogen Storage Disease Type I --- Signal Transduction --- 577.32 --- 577.3 --- 577.3 Physical and physicochemical bases of life. Biophysics. Biophysical chemistry in general --- Physical and physicochemical bases of life. Biophysics. Biophysical chemistry in general --- 577.32 Molecular biophysics --- Molecular biophysics --- Congresses --- physiology --- Animal physiology. Animal biophysics --- Congresses. --- G proteins - Congresses. --- Cellular signal transduction - Congresses.

Bioinformatics: sequence and genome analysis
Author:
ISBN: 0879696087 0879696559 9780879696559 0879695978 9780879695972 9780879696085 9781603273169 1603273166 9781603273176 1603273174 Year: 2001 Publisher: New York Cold Spring Harbor Laboratory

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The G protein-coupled receptors (GPCRs), known to be one of the largest superfamilies in the human genome, underpin a multitude of physiological processes and represent a significant target for bioactive and drug discovery programs. In G Protein-Coupled Receptors in Drug Discovery: Methods and Protocols, experts in the field provide a range of classic and cutting-edge laboratory protocols developed for GPCR research, as well as several current review articles relevant to the area of high throughput GPCR screening, with discussion on GPCR structure and GPCR signalling. Written in the highly successful Methods in Molecular Biology™ series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and easy to use, G Protein-Coupled Receptors in Drug Discovery: Methods and Protocols serves to aid all those who wish to further the vital research in their GPCR drug discovery programs.

Keywords

Molecular biology --- Computational Biology. --- Sequence Analysis, DNA. --- Base Sequence. --- Sequence Analysis, RNA. --- Genetics --- Bioinformatics. --- Nucleotide sequence. --- Amino acid sequence. --- Génétique --- Bio-informatique --- Séquence nucléotidique --- Séquence des acides aminés --- Data processing. --- Informatique --- Bioinformatics --- Amino acid sequence --- Data processing --- -Nucleotide sequence --- #TELE:SISTA --- Analysis, Nucleic acid sequence --- Analysis, Nucleotide sequence --- Base sequence (Nucleic acids) --- DNA sequence --- Nucleic acid sequence analysis --- Nucleotide sequence analysis --- RNA sequence --- Sequence, Nucleotide --- Nucleic acids --- Nucleotides --- Sequence alignment (Bioinformatics) --- Biology --- Embryology --- Mendel's law --- Adaptation (Biology) --- Breeding --- Chromosomes --- Heredity --- Mutation (Biology) --- Variation (Biology) --- Bio-informatics --- Biological informatics --- Information science --- Computational biology --- Systems biology --- Amino acid sequence analysis --- Analysis, Amino acid sequence --- Peptide sequence --- Peptide sequencing --- Protein sequence --- Protein sequencing --- Sequence, Amino acid --- Amino acids --- Proteins --- Analysis --- Génétique --- Séquence nucléotidique --- Séquence des acides aminés --- Nucleotide sequence --- 57.087 --- 57.087 Methods and techniques for parameter estimation. Recording of biological data --- Methods and techniques for parameter estimation. Recording of biological data --- G proteins --- Drug development --- Receptors, G-Protein-Coupled --- Drug Discovery --- 577.122 --- 577.122 Protein metabolism --- Protein metabolism --- Drug Prospecting --- Discovery, Drug --- Prospecting, Drug --- High-Throughput Screening Assays --- Bioprospecting --- G Protein Coupled Receptor --- G-Protein-Coupled Receptor --- G-Protein-Coupled Receptors --- G Protein Coupled Receptors --- Receptor, G-Protein-Coupled --- Receptors, G Protein Coupled --- Development of drugs --- Drugs --- New drug development --- Pharmacology --- Pharmacy --- GTP-binding proteins --- GTP regulatory proteins --- Guanine nucleotide-binding proteins --- Guanine nucleotide regulatory proteins --- Membrane proteins --- Receptors --- Development --- Toxicology. --- Pharmacology/Toxicology. --- Chemicals --- Medicine --- Poisoning --- Poisons --- Toxicology --- Genetics - Data processing

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