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The gene responsible for Dyggve-Melchior-Clausen syndrome encodes a novel peripheral membrane protein dynamically associated with the Golgi apparatus

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The gene responsible for Dyggve-Melchior-Clausen syndrome encodes a novel peripheral membrane protein dynamically associated with the Golgi apparatus. / Dimitrov, Ariane; Paupe, Vincent; Gueudry, Charles; Sibarita, Jean-Baptiste; Raposo, Graça; Vielemeyer, Ole; Gilbert, Thierry; Csaba, Zsolt; Attie-Bitach, Tania; Cormier-Daire, Valérie; Gressens, Pierre; Rustin, Pierre; Perez, Franck; El Ghouzzi, Vincent.

In: Human Molecular Genetics, Vol. 18, No. 3, N/A, 01.02.2009, p. 440-453.

Research output: Contribution to journalArticle

Harvard

Dimitrov, A, Paupe, V, Gueudry, C, Sibarita, J-B, Raposo, G, Vielemeyer, O, Gilbert, T, Csaba, Z, Attie-Bitach, T, Cormier-Daire, V, Gressens, P, Rustin, P, Perez, F & El Ghouzzi, V 2009, 'The gene responsible for Dyggve-Melchior-Clausen syndrome encodes a novel peripheral membrane protein dynamically associated with the Golgi apparatus', Human Molecular Genetics, vol. 18, no. 3, N/A, pp. 440-453. https://doi.org/10.1093/hmg/ddn371

APA

Dimitrov, A., Paupe, V., Gueudry, C., Sibarita, J-B., Raposo, G., Vielemeyer, O., Gilbert, T., Csaba, Z., Attie-Bitach, T., Cormier-Daire, V., Gressens, P., Rustin, P., Perez, F., & El Ghouzzi, V. (2009). The gene responsible for Dyggve-Melchior-Clausen syndrome encodes a novel peripheral membrane protein dynamically associated with the Golgi apparatus. Human Molecular Genetics, 18(3), 440-453. [N/A]. https://doi.org/10.1093/hmg/ddn371

Vancouver

Dimitrov A, Paupe V, Gueudry C, Sibarita J-B, Raposo G, Vielemeyer O et al. The gene responsible for Dyggve-Melchior-Clausen syndrome encodes a novel peripheral membrane protein dynamically associated with the Golgi apparatus. Human Molecular Genetics. 2009 Feb 1;18(3):440-453. N/A. https://doi.org/10.1093/hmg/ddn371

Author

Dimitrov, Ariane ; Paupe, Vincent ; Gueudry, Charles ; Sibarita, Jean-Baptiste ; Raposo, Graça ; Vielemeyer, Ole ; Gilbert, Thierry ; Csaba, Zsolt ; Attie-Bitach, Tania ; Cormier-Daire, Valérie ; Gressens, Pierre ; Rustin, Pierre ; Perez, Franck ; El Ghouzzi, Vincent. / The gene responsible for Dyggve-Melchior-Clausen syndrome encodes a novel peripheral membrane protein dynamically associated with the Golgi apparatus. In: Human Molecular Genetics. 2009 ; Vol. 18, No. 3. pp. 440-453.

Bibtex Download

@article{34ad27ee2a454204b29d1a702faafe20,
title = "The gene responsible for Dyggve-Melchior-Clausen syndrome encodes a novel peripheral membrane protein dynamically associated with the Golgi apparatus",
abstract = "Dyggve-Melchior-Clausen dysplasia (DMC) is a rare inherited dwarfism with severe mental retardation due to mutations in the DYM gene which encodes Dymeclin, a 669-amino acid protein of yet unknown function. Despite a high conservation across species and several predicted transmembrane domains, Dymeclin could not be ascribed to any family of proteins. Here we show, using in situ hybridization, that DYM is widely expressed in human embryos, especially in the cortex, the hippocampus and the cerebellum. Both the endogenous and the recombinant protein fused to green fluorescent protein co-localized with Golgi apparatus markers. Electron microscopy revealed that Dymeclin associates with the Golgi apparatus and with transitional vesicles of the reticulum-Golgi interface. Moreover, permeabilization assays revealed that Dymeclin is not a transmembrane but a peripheral protein of the Golgi apparatus as it can be completely released from the Golgi after permeabilization of the plasma membrane. Time lapse confocal microscopy experiments on living cells further showed that the protein shuttles between the cytosol and the Golgi apparatus in a highly dynamic manner and recognizes specifically a subset of mature Golgi membranes. Finally, we found that DYM mutations associated with DMC result in mis-localization and subsequent degradation of Dymeclin. These data indicate that DMC results from a loss-of-function of Dymeclin, a novel peripheral membrane protein which shuttles rapidly between the cytosol and mature Golgi membranes and point out a role of Dymeclin in cellular trafficking.",
keywords = "Brain, Cell Line, Cytosol, Dwarfism, Embryo, Mammalian, Golgi Apparatus, Humans, Membrane Proteins, Mutation, Protein Transport, Proteins",
author = "Ariane Dimitrov and Vincent Paupe and Charles Gueudry and Jean-Baptiste Sibarita and Gra{\c c}a Raposo and Ole Vielemeyer and Thierry Gilbert and Zsolt Csaba and Tania Attie-Bitach and Val{\'e}rie Cormier-Daire and Pierre Gressens and Pierre Rustin and Franck Perez and {El Ghouzzi}, Vincent",
year = "2009",
month = feb,
day = "1",
doi = "10.1093/hmg/ddn371",
language = "English",
volume = "18",
pages = "440--453",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "3",

}

RIS (suitable for import to EndNote) Download

TY - JOUR

T1 - The gene responsible for Dyggve-Melchior-Clausen syndrome encodes a novel peripheral membrane protein dynamically associated with the Golgi apparatus

AU - Dimitrov, Ariane

AU - Paupe, Vincent

AU - Gueudry, Charles

AU - Sibarita, Jean-Baptiste

AU - Raposo, Graça

AU - Vielemeyer, Ole

AU - Gilbert, Thierry

AU - Csaba, Zsolt

AU - Attie-Bitach, Tania

AU - Cormier-Daire, Valérie

AU - Gressens, Pierre

AU - Rustin, Pierre

AU - Perez, Franck

AU - El Ghouzzi, Vincent

PY - 2009/2/1

Y1 - 2009/2/1

N2 - Dyggve-Melchior-Clausen dysplasia (DMC) is a rare inherited dwarfism with severe mental retardation due to mutations in the DYM gene which encodes Dymeclin, a 669-amino acid protein of yet unknown function. Despite a high conservation across species and several predicted transmembrane domains, Dymeclin could not be ascribed to any family of proteins. Here we show, using in situ hybridization, that DYM is widely expressed in human embryos, especially in the cortex, the hippocampus and the cerebellum. Both the endogenous and the recombinant protein fused to green fluorescent protein co-localized with Golgi apparatus markers. Electron microscopy revealed that Dymeclin associates with the Golgi apparatus and with transitional vesicles of the reticulum-Golgi interface. Moreover, permeabilization assays revealed that Dymeclin is not a transmembrane but a peripheral protein of the Golgi apparatus as it can be completely released from the Golgi after permeabilization of the plasma membrane. Time lapse confocal microscopy experiments on living cells further showed that the protein shuttles between the cytosol and the Golgi apparatus in a highly dynamic manner and recognizes specifically a subset of mature Golgi membranes. Finally, we found that DYM mutations associated with DMC result in mis-localization and subsequent degradation of Dymeclin. These data indicate that DMC results from a loss-of-function of Dymeclin, a novel peripheral membrane protein which shuttles rapidly between the cytosol and mature Golgi membranes and point out a role of Dymeclin in cellular trafficking.

AB - Dyggve-Melchior-Clausen dysplasia (DMC) is a rare inherited dwarfism with severe mental retardation due to mutations in the DYM gene which encodes Dymeclin, a 669-amino acid protein of yet unknown function. Despite a high conservation across species and several predicted transmembrane domains, Dymeclin could not be ascribed to any family of proteins. Here we show, using in situ hybridization, that DYM is widely expressed in human embryos, especially in the cortex, the hippocampus and the cerebellum. Both the endogenous and the recombinant protein fused to green fluorescent protein co-localized with Golgi apparatus markers. Electron microscopy revealed that Dymeclin associates with the Golgi apparatus and with transitional vesicles of the reticulum-Golgi interface. Moreover, permeabilization assays revealed that Dymeclin is not a transmembrane but a peripheral protein of the Golgi apparatus as it can be completely released from the Golgi after permeabilization of the plasma membrane. Time lapse confocal microscopy experiments on living cells further showed that the protein shuttles between the cytosol and the Golgi apparatus in a highly dynamic manner and recognizes specifically a subset of mature Golgi membranes. Finally, we found that DYM mutations associated with DMC result in mis-localization and subsequent degradation of Dymeclin. These data indicate that DMC results from a loss-of-function of Dymeclin, a novel peripheral membrane protein which shuttles rapidly between the cytosol and mature Golgi membranes and point out a role of Dymeclin in cellular trafficking.

KW - Brain

KW - Cell Line

KW - Cytosol

KW - Dwarfism

KW - Embryo, Mammalian

KW - Golgi Apparatus

KW - Humans

KW - Membrane Proteins

KW - Mutation

KW - Protein Transport

KW - Proteins

U2 - 10.1093/hmg/ddn371

DO - 10.1093/hmg/ddn371

M3 - Article

C2 - 18996921

VL - 18

SP - 440

EP - 453

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 3

M1 - N/A

ER -

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