Matrilin-3 mutations that cause chondrodysplasias interfere with protein trafficking while a mutation associated with hand osteoarthritis does not.

ABSTRACT: Several mutations in the extracellular matrix protein matrilin-3 cause a heterogeneous disease spectrum affecting skeletal tissues. We introduced three disease causing point mutations leading to single amino acid exchanges (R116W, T298M, C299S) in matrilin-3 and expressed the corresponding proteins in primary articular chondrocytes to elucidate pathogenic mechanisms at the cellular level. Expression levels, processing, and the secretion pattern of a mutation linked to hand osteoarthritis (T298M) were similar to the wildtype protein, whereas the two other mutants were poorly expressed and hardly detectable in supernatants of transiently transfected cells. Using immunofluorescence staining, we demonstrated that mutants R116W and C299S are retained and accumulate within the endoplasmatic reti

SUBMITTER: Otten C 

PROVIDER: S-EPMC1735938 | biostudies-literature | 2005 Oct

REPOSITORIES: biostudies-literature