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- Title
Abnormal trafficking of sarcolemmal proteins in α-glucosidase deficiency.
- Authors
Radojevic, V.; Humm, A. M.; Rösler, K. M.; Lauterburg, T.; Burgunder, J-M.
- Abstract
The dystrophin-associated protein complex (DAP) plays an important role in the integrity and stability of the muscle membrane. Whereas much is known about the interaction between DAP members at the sarcolemmal location, intracellular DAP assembly and trafficking is still largely unknown. In α-glucosidase (acid maltase) deficiency (αGDD), accumulation of glycogen is accompanied by cytoarchitectural abnormalities impairing normal protein metabolism. In the present study, we took advantage of this fact to examine the consequences of impaired protein handling on the formation of DAP, with the aim of gaining indirect knowledge about its sarcoplasmic trafficking and a better understanding of mechanisms leading to myopathic changes found in αGDD. Histological examination of αGDD muscle confirmed a vacuolar myopathy with glycogen accumulation both in vacuoles and within the sarcoplasm. Sarcoplasmic accumulation of sarcolemmal proteins, including dystrophin and sarcoglycans, occurred around some vacuoles and within non-vacuolated fibres. Utrophin was up-regulated and found at extra-junctional sarcolemmal locations of many fibres. αGDD muscle cells developed in a fashion similar to that of controls in culture. However, vacuoles were found in 2-week-old αGDD myotubes, and these subsequently increased in size and number. Substantial alterations in DAP handling were found, with accumulation close to the Golgi apparatus. Utrophin was not enriched in the sarcoplasm but was up-regulated along the whole sarcolemma. Our results demonstrate a close association of dystrophin and sarcoglycans during sarcoplasmic processing. Furthermore, they suggest that the myopathy found in αGDD is a secondary form of DAP deficiency.
- Subjects
DYSTROPHIN; MEMBRANE proteins; MUSCLES; SARCOLEMMA
- Publication
Acta Neuropathologica, 2003, Vol 105, Issue 4, p373
- ISSN
0001-6322
- Publication type
Article
- DOI
10.1007/s00401-002-0656-z