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.
Department of Microbiology and Immunology, Vanderbilt University School of Medicine, 1161 21st Ave. South, Nashville, TN 37232-2363, USA. anna.osipovich@vanderbilt.edu
Anna B
AB
Osipovich
Jennifer L
JL
Jennings
Qing
Q
Lin
Andrew J
AJ
Link
H Earl
HE
Ruley
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