TY - JOUR
T1 - Genetic diseases of connective tissues: Cellular and extracellular effects of ECM mutations
AU - Bateman, John F.
AU - Boot-Handford, Raymond P.
AU - Lamandé, Shireen R.
PY - 2009/3
Y1 - 2009/3
N2 - Tissue-specific extracellular matrices (ECMs) are crucial for normal development and tissue function, and mutations in ECM genes result in a wide range of serious inherited connective tissue disorders. Mutations cause ECM dysfunction by combinations of two mechanisms. First, secretion of the mutated ECM components can be reduced by mutations affecting synthesis or by structural mutations causing cellular retention and/or degradation. Second, secretion of mutant protein can disturb crucial ECM interactions, structure and stability. Moreover, recent experiments suggest that endoplasmic reticulum (ER) stress, caused by mutant misfolded ECM proteins, contributes to the molecular pathology. Targeting ER stress might offer a new therapeutic strategy. © 2009 Macmillan Publishers Limited. All rights reserved.
AB - Tissue-specific extracellular matrices (ECMs) are crucial for normal development and tissue function, and mutations in ECM genes result in a wide range of serious inherited connective tissue disorders. Mutations cause ECM dysfunction by combinations of two mechanisms. First, secretion of the mutated ECM components can be reduced by mutations affecting synthesis or by structural mutations causing cellular retention and/or degradation. Second, secretion of mutant protein can disturb crucial ECM interactions, structure and stability. Moreover, recent experiments suggest that endoplasmic reticulum (ER) stress, caused by mutant misfolded ECM proteins, contributes to the molecular pathology. Targeting ER stress might offer a new therapeutic strategy. © 2009 Macmillan Publishers Limited. All rights reserved.
U2 - 10.1038/nrg2520
DO - 10.1038/nrg2520
M3 - Article
C2 - 19204719
SN - 1471-0056
VL - 10
SP - 173
EP - 183
JO - Nature Reviews Genetics
JF - Nature Reviews Genetics
IS - 3
ER -