The gene responsible for Dyggve-Melchior-Clausen syndrome encodes a novel peripheral membrane protein dynamically associated with the Golgi apparatus
1. Hum Mol Genet. 2009 Feb 1;18(3):440-53. doi: 10.1093/hmg/ddn371. Epub 2008 Nov 7.
The gene responsible for Dyggve-Melchior-Clausen syndrome encodes a novel
peripheral membrane protein dynamically associated with the Golgi apparatus.
Dimitrov A(1), Paupe V, Gueudry C, Sibarita JB, Raposo G, Vielemeyer O, Gilbert
T, Csaba Z, Attie-Bitach T, Cormier-Daire V, Gressens P, Rustin P, Perez F, El
Ghouzzi V.
Author information:
(1)UMR CNRS 144, Institut Curie, 75005 Paris, France.
Erratum in
Hum Mol Genet. 2009 May 1;18(9):1714-6.
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.
DOI: 10.1093/hmg/ddn371
PMID: 18996921 [Indexed for MEDLINE]