Dyggve-Melchior-Clausen syndrome: chondrodysplasia resulting from defects in intracellular vesicle traffic.
Dyggve-Melchior-Clausen syndrome and Smith-McCort dysplasia are recessive spondyloepimetaphyseal dysplasias caused by loss-of-function mutations in dymeclin (Dym), a gene with previously unknown function. Here we report that Dym-deficient mice display defects in endochondral bone formation similar to that of Dyggve-Melchior-Clausen syndrome and Smith-McCort dysplasia, demonstrating functional conservation between the two species. Dym-mutant cells display multiple defects in vesicle traffic, as evidenced by enhanced dispersal of Golgi markers in interphase cells, delayed Golgi reassembly after brefeldin A treatment, delayed retrograde traffic of an endoplasmic reticulum-targeted Shiga toxin B subunit, and altered furin trafficking; and the Dym protein associates with multiple cellular proteins involved in vesicular traffic. These results establish dymeclin as a novel protein involved in Golgi organization and intracellular vesicle traffic and clarify the molecular basis for chondrodysplasia in mice and men.
Osipovich
Anna B
AB
Department of Microbiology and Immunology, Vanderbilt University School of Medicine, 1161 21st Ave. South, Nashville, TN 37232-2363, USA. anna.osipovich@vanderbilt.edu
Jennings
Jennifer L
JL
Lin
Qing
Q
Link
Andrew J
AJ
Ruley
H Earl
HE
D000818:Animals; D001692:Biological Transport; D002478:Cells, Cultured; D002806:Chondrodysplasia Punctata / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D022162:Cytoplasmic Vesicles / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009154:Mutation / Q000235:genetics; D011485:Protein Binding; D013577:Syndrome
C532993:Dym protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins