Dyggve-Melchior-Clausen syndrome: chondrodysplasia resulting from defects in intracellular vesicle traffic.

Osipovich AB, Jennings JL, Lin Q, Link AJ, Ruley HE
Proc Natl Acad Sci U S A. 2008 105 (42): 16171-6

PMID: 18852472 · PMCID: PMC2571016 · DOI:10.1073/pnas.0804259105

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.

MeSH Terms (11)

Animals Biological Transport Cells, Cultured Chondrodysplasia Punctata Cytoplasmic Vesicles Humans Membrane Proteins Mice Mutation Protein Binding Syndrome

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