Dystroglycan: a multifunctional adaptor protein

Higginson, J.R. and Winder, S.J. (2005) Dystroglycan: a multifunctional adaptor protein. Biochemical Society Transactions, 33, pp. 1254-1255. (doi: 10.2174/157436211794109424)

Abstract

Dystroglycan (DG) is a ubiquitous membrane-spanning cell adhesion molecule and forms a crucial link between the extracellular matrix (ECM) and actin cytoskeleton. DG is composed of two proteins α- and β- DG which are encoded by a single gene. It was originally identified as the extracellular and transmembrane constituents of a large oligomeric complex of sarcolemmal proteins associated with dystrophin, the protein product of the Duchenne muscular dystrophy gene. Mutations of the components of this complex are associated with several forms of severe muscular dystrophies. DG is also expressed in the neuromuscular junction and non-muscle tissues such as brain, peripheral nerve, retina and kidney. With a broad expression pattern and multiple interacting proteins, DG is now thought to be important not only as a structural molecule but also as a cell signaling molecule, playing roles in cytoskeletal reorganization such as early development, myelinogenesis, synaptogenesis, epithelial morphogenesis and angiogenesis. Defective glycosylation of α-DG caused by mutations of several glycosyltransferases leads to the disruption of its linkage to the ECM. This aberrant glycosylation of α-DG is now considered as a universal pathogenic mechanism of neuromuscular diseases, especially congenital muscular dystrophies. Recently, we reported that the extracellular domain of β-DG is cleaved by matrix metalloproteinase (MMP)-2 and MMP-9, raising a possibility of therapy for muscular dystrophy by blocking MMP activity. We also demonstrated that the N-terminal domain of extracellular α-DG (α-DG-N) is cleaved by a proprotein convertase and secreted into body fluid in the physiological state. These findings imply that the cleaved α-DG fragment may play an important biological role in various tissues. Here, we review the current understanding of diverging roles of DG and its implications in therapy for neuromuscular diseases.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: UNSPECIFIED
• Authors: Higginson, J.R., and Winder, S.J.
• College/School: College of Medical Veterinary and Life Sciences
• Journal Name: Biochemical Society Transactions
• ISSN: 1575-3624
• ISSN (Online): 1574-3623