Dystroglycan

The lepromatous form of leprosy is characterized by loss ofcutaneoussensibility. Hansen sbacillus(Mycobacterium leprae), which proliferates only in environments cooler than the core temperature maintained by most mammals, is capable of infecting Schwann cells in subcutaneous nerves because the basal lamina of these cells contains a-dystroglycan, to which this mycobacterium binds, and because subcutaneous nerves are often cooler than deeper tissues. Lepromatous neuropathy is a common cause of sensory mononeuropathy multiplex in the developing World [16,17]. 

Rambukkana, A., Yamada, H., Zanazzi, G. et al. Role of alpha-dystroglycan as a Schwann cell receptor for Mycobacterium leprae. Science 282 2076-2070,1998. 

Other human O-glycosylation deficiencies that are not detectable by IEF of ApoC-III affect oligosaccharides in O-mannosidic linkage to a-dystroglycan in Walker-Warburg syndrome and muscle-eye-brain disease [2, 32], and fucosylated N- and... 

While one end of the dystrophin molecule binds to actin filaments, the C-terminal domain associates with several additional proteins to form a dystrophin-glycoprotein complex (see figure)/1 k Dystrophin is linked directly to the membrane-spanning protein P-dystroglycan, which in the outer membrane surfaces associates with a glycoprotein a-dystroglycan. The latter binds to laminin-2 (Fig. 8-33), a protein that binds the cell to the basal lamina. Four... 

SH3 domains are used extensively by cytoskeletal and signaling proteins to mediate protein-protein interactions, and they do so through a proline-rich motif. This has a consensus sequence P-X-X-P. Another motif—the WW domain—also facilitates protein-protein interactions, and it too is based on proline. Its consensus sequence is P-P-X-Y (a Type I WW repeat as identified in the extracellular matrix receptor /3-dystroglycan) and this interacts with a WW domain in dystrophin or utrophin (Ilsley et al, 2002 Winder, 2001). These two motifs are interesting, not only because they are short and proline-rich, but because they are able to impose considerable specificity of interaction on the proteins involved. 

Within the skeletal musculature, dystrophin plays an important role in maintaining the integrity of the sarcolemmal membrane. Dystrophin is not able to perform this task alone and interacts with a number of other proteins that include dystroglycans, sarcoglycans, dystrobrevins, syntrophins, and sarcospan (Straub and Campbell, 1997). Mutation of dystrophin or, indeed,... 

As mentioned above, the WW domain is another example of a protein-protein interaction module that binds proline-rich sequences (Kay et al., 2000). Dystrophin and utrophin WW domains interact predominantly with the extracellular matrix receptor dystroglycan, which contains a type 1 WW motif of consensus PPxY (reviewed in Ilsley et al., 2002 Winder, 2001). A structure of a WW domain from dystrophin was solved recently as part of a structure including the EF-hand region, and also with and without a bound /3-dystroglycan peptide (Huang et al., 2000). 

Chung, W., and Campanelli, J. T. (1999). WW and EF hand domains of dystrophin-family proteins mediate dystroglycan binding. Mol. Cell Biol. Res. Commun. 2, 162-171. 

Ishikawa-Sakiirai, M., Yoshida, M., Imamura, M., Davies, K. E., and Ozawa, E. (2004). ZZ domain is essentially required for the physiological binding of dystrophin and utrophin to beta-dystroglycan. Hum. Mol. Genet. 13, 693-702. 

James, M., Nuttall, A., Ilsley, J. L., Ottersbach, K., Tinsley, J. M., Sudol, M., and Winder, S. J. (2000). Adhesion-dependent tyrosine phosphorylation of (beta)-dystroglycan regulates its interaction with utrophin./. Cell Sci. 113, 1717-1726. 

Jung, D., Yang, B., Meyer, J., Chamberlain,J. S., and Campbell, K. P. (1995). Identification and characterization of the dystrophin anchoring site on beta-dystroglycan. / Biol. Chem. 270, 27305-27310. 

Lenk, U., Oexle, K., Voit, T., Ancker, U., Hellner, K. A., Speer, A., and Hubner, C. (1996). A cysteine 3340 substitution in the dystroglycan-binding domain of dystrophin associated with Duchenne muscular dystrophy, mental retardation and absence of the ERG b-wave. Hum. Mol. Genet. 5, 973-975. 

Rentschler, S., Linn, H., Deininger, K., Bedford, M. T., Espanel, X., and Sudol, M. (1999). The WW domain of dystrophin requires EF-hands region to interact with beta-dystroglycan. Biol. Chem. 380, 431-442. 

The last 15 amino acids of (3-dystroglycan appear to bind directly to the cysteine-rich region of dystrophin. This region of (3-dystroglycan is proline rich and contains a site for tyrosine phosphorylation (James et al., 2000). Recently, the crystal structure of (3-dystroglycan bound to dystrophin has been determined (Huang et al.,... 

Ibraghimov-Beskrovnaya, O., Milatovich, A., Ozcelik, T., Yang, B., Koepnick, K., Francke, U., and Campbell, K.P., 1993, Human dystroglycan skeletal muscle cDNA, genomic structure, origin of tissue specific isoforms and chromosomal localization, Hum Mol Genet, 2, pp 1651—1657. 

Rosa, G., Ceccarini, M., Cavaldesi, M., Zini, M., and Petrucci, T.C., 1996, Localization of the dystrophin binding site at the carboxyl terminus of beta-dystroglycan, Biochem Biophys Res Commun, 223, pp 272-277. 

Smalheiser, N.R., and Kim, E., 1995, Purification of cranin, a laminin binding membrane protein. Identity with dystroglycan and reassessment of its carbohydrate moieties, J Biol Chem, 270, pp 15425-15433. 

Pereboev, A. V., Ahmed, N., Nguyen thi Man, and Morris, G. E. (2001) Epitopes in the interacting regions of beta-dystroglycan (PPxY motif) and dystrophin (WW domain). Biochim. Biophys. Acta. 527, 54-60. 

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