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O-Mannosylation and human disease

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Abstract

Glycosylation of proteins is arguably the most prevalent co- and post-translational modification. It is responsible for increased heterogeneity and functional diversity of proteins. Here we discuss the importance of one type of glycosylation, specifically O-mannosylation and its relationship to a number of human diseases. The most widely studied O-mannose modified protein is alpha-dystroglycan (α-DG). Recent studies have focused intensely on α-DG due to the severity of diseases associated with its improper glycosylation. O-mannosylation of α-DG is involved in cancer metastasis, arenavirus entry, and multiple forms of congenital muscular dystrophy [1, 2]. In this review, we discuss the structural and functional characteristics of O-mannose-initiated glycan structures on α-DG, enzymes involved in the O-mannosylation pathway, and the diseases that are a direct result of disruptions within this pathway.

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Acknowledgments

We would like to thank all members of the Wells’ laboratory for helpful discussions. We apologize to any laboratories that have contributed to this growing field that we failed to cite. This work was supported in part by grants from the NIH (P41RR018502 and R21AR056055, L.W. co-PI).

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  1. Department of Biochemistry and Molecular Biology, Complex Carbohydrate Research Center, University of Georgia, Athens, GA, USA

    Christina M. Dobson, Samuel J. Hempel, Stephanie H. Stalnaker, Ryan Stuart & Lance Wells

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  1. Christina M. Dobson
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Correspondence to Lance Wells.

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Dobson, C.M., Hempel, S.J., Stalnaker, S.H. et al. O-Mannosylation and human disease. Cell. Mol. Life Sci. 70, 2849–2857 (2013). https://doi.org/10.1007/s00018-012-1193-0

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