Membrane Trafficking to the Extracellular Matrix and Skeletal Dysplasia

The bone extracellular matrix (ECM) is composed mainly of collagen fibrils and many non-collagenous proteins. A large number of skeletal dysplasias are caused by disruption of the ECM architecture due to the mutation of some of these ECM components, particularly collagen, which not only disrupts the bone structure but also alters signaling pathways that emanate from the ECM. Rather than being a static entity, the ECM exhibits dynamic movement and turnover that have important regulatory and structural consequences for bone development and maintenance. The construction and turnover of the ECM relies on the transport of ECM components by membrane trafficking: as a consequence, disruption of the membrane trafficking machinery can also lead to skeletal dysplasia. Here we provide an overview of the mechanisms by which mutations of some of the secretory trafficking machinery lead to human skeletal dysplasia.