Xylose phosphatase activity of dystroglycan self-regulates its receptor function

Ishita Chandel; David Venzke; Bailey A Wollesen; Liping Yu; Kevin P Campbell

doi:10.1126/science.adz7427

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Xylose phosphatase activity of dystroglycan self-regulates its receptor function

Journal article

Peer reviewed

Xylose phosphatase activity of dystroglycan self-regulates its receptor function

Ishita Chandel, David Venzke, Bailey A Wollesen, Liping Yu and Kevin P Campbell

Science (American Association for the Advancement of Science), Vol.393(6812), pp.690-695

08/13/2026

DOI: 10.1126/science.adz7427

PMID: 42594207

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Abstract

Dystroglycan (DG) is an extracellular matrix receptor crucial for tissue development and pathogen entry. DG harbors a long, complex glycan called matriglycan. Loss of matriglycan or reduction in its length disrupts DG function, causing dystroglycanopathies. However, the mechanism regulating matriglycan length is unknown. In this study, we found that a xylose kinase facilitated the initiation of matriglycan synthesis by adding a phosphate to the xylose of the matriglycan primer. Matriglycan elongation occurred when the phosphate was removed by the N-terminal domain of DG (DGN). DGN has the conserved DXDXT/V active site motif found in haloacid dehalogenase domains of phosphohydrolases. Mutations in this site abolished DGN phosphatase activity, reduced matriglycan length, and caused muscle disease in mice. Thus, DG has an unexpected xylose phosphatase function involved in regulating matriglycan extension.

Mutation

Animals

Catalytic Domain

Dystroglycans - chemistry

Dystroglycans - genetics

Dystroglycans - metabolism

Humans

Mice

Phosphoric Monoester Hydrolases - chemistry

Phosphoric Monoester Hydrolases - genetics

Phosphoric Monoester Hydrolases - metabolism

Xylose - metabolism

Details

Title: Subtitle: Xylose phosphatase activity of dystroglycan self-regulates its receptor function
Creators: Ishita Chandel - University of Iowa
David Venzke - University of Iowa
Bailey A Wollesen - University of Iowa
Liping Yu - University of Iowa
Kevin P Campbell - University of Iowa
Resource Type: Journal article
Publication Details: Science (American Association for the Advancement of Science), Vol.393(6812), pp.690-695
DOI: 10.1126/science.adz7427
PMID: 42594207
ISSN: 1095-9203
eISSN: 1095-9203
Publisher: AAAS
Language: English
Date published: 08/13/2026
Academic Unit: Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Medicine Administration
Record Identifier: 9985218636302771

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