From Muscle to Brain: A Study of Dystroglycan

The dystroglycans (DGs), and -DG, form the core of the dystrophin glycoprotein complex in the skeletal muscle as a transmembrane linkage between the cytoskeleton and the extracellular matrix. Disruption of this linkage leads to muscular dystrophy. DG is also implicated in synaptogenesis of the neuromuscular junction. In the central nervous system (CNS), however, roles of DG remain largely unknown. As a step toward revealing the function of DG in the CNS, affinity-purified rabbit antisera against -DG were raised and tested, which recognize only DG in brain extracts. Immunocytochemistry with the sera found in cultured rat hippocampal neurons DG is expressed in cell bodies, dendrites and axons and forms clusters at some dendritic spines and is colocalized with synaptophysin. Immunoaffinity purification revealed that -DG is associated with -DG in rat hippocampus, but the isoforms of dystrophin and utrophin are undetectable. In Coomassie-blue stained gels, in addition to -DG, a band of about 100 kD was also found. This band does not match any proteins known to interact with -DG and its identity and function could uncover a new role of DG complex in the CNS.

Autorentext

Yougen Zhan obtained his Bachelor of Medicine from Beijing Medical University and did his residency in Diagnostic Radiology. He was a fellow in the Radiology Department of the Johns Hopkins Hospital. He obtained his M.Sc. and Ph.D. in neurological sciences from McGill University. He is currently a fellow in Harvard Medical School.

Klappentext

The dystroglycans (DGs), a and ß-DG, form the core of the dystrophin glycoprotein complex in the skeletal muscle as a transmembrane linkage between the cytoskeleton and the extracellular matrix. Disruption of this linkage leads to muscular dystrophy. DG is also implicated in synaptogenesis of the neuromuscular junction. In the central nervous system (CNS), however, roles of DG remain largely unknown. As a step toward revealing the function of DG in the CNS, affinity-purified rabbit antisera against ß-DG were raised and tested, which recognize only DG in brain extracts. Immunocytochemistry with the sera found in cultured rat hippocampal neurons DG is expressed in cell bodies, dendrites and axons and forms clusters at some dendritic spines and is colocalized with synaptophysin. Immunoaffinity purification revealed that ß-DG is associated with a-DG in rat hippocampus, but the isoforms of dystrophin and utrophin are undetectable. In Coomassie-blue stained gels, in addition to ß-DG, a band of about 100 kD was also found. This band does not match any proteins known to interact with ß-DG and its identity and function could uncover a new role of DG complex in the CNS.