5th de Duve Lecture: Watch the podcast!
Pascale Cossart enlightens us on the molecular and cellular bases of bacterial infections.
The protein alpha-dystroglycan plays an important role in linking the intracellular cytoskeleton to the extracellular matrix. For this function, it needs to be glycosylated in a process that involves at least 12 enzymes. Mutations in any of these enzymes lead to muscle and brain diseases of varying severity, for which no therapy currently exists. At present, the precise structure of the glycan and the function of some enzymes involved in its assembly are still incompletely understood.
In an article published in Nature Communications, the authors reveal the function of three enzymes required for alpha-dystroglycan glycosylation - ISPD, FKTN and FKRP. The three enzymes are working together to attach a sugar derivative (ribitol) together with a phosphate group onto the glycan of alpha-dystroglycan. While similar structures are often encountered in the capsules of bacteria, these structures were not known to exist in eukaryotes before.
Notably, cells from some patients with ISPD mutations partially or completely restore alpha-dystroglycan glycosylation when ribitol is added to the medium. This indicates that dietary supplementation with ribitol should be evaluated as therapeutic approach for a subset of patients with ISPD mutations.
Article describing this research
Gerin I, Ury B, Breloy I, Bouchet-Seraphin C, Bolsée J, Halbout M, Graff J, Vertommen D, Muccioli GG, Seta N, Cuisset JM, Dabaj I, Quijano-Roy S, Grahn A, Van Schaftingen E, Bommer GT.
Nature Communications (2016), 7:11534.