Laforin, a Dual Specificity Phosphatase That Dephosphorylates Complex Carbohydrates

• Published in: The Journal of biological chemistry 2006-10, Vol.281 (41), p.30412-30418
• Main Authors: Worby, Carolyn A., Gentry, Matthew S., Dixon, Jack E.
• Format: Article
• Language: English
• Subjects: Adenoviridae - metabolism; Amino Acid Sequence; Animals; Carbohydrates - chemistry; CHO Cells; Cricetinae; Glycogen Synthase Kinase 3 - metabolism; Glycogen Synthase Kinase 3 beta; Humans; Molecular Sequence Data; Neurodegenerative Diseases - metabolism; Protein Tyrosine Phosphatases - chemistry; Protein Tyrosine Phosphatases, Non-Receptor; Sequence Homology, Amino Acid; Transfection
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M606117200

Laforin is the only phosphatase in the animal kingdom that contains a carbohydrate-binding module. Mutations in the gene encoding laforin result in Lafora disease, a fatal autosomal recessive neurodegenerative disorder, which is diagnosed by the presence of intracellular deposits of insoluble complex carbohydrates known as Lafora bodies. We demonstrate that laforin interacts with proteins known to be involved in glycogen metabolism and rule out several of these proteins as potential substrates. Surprisingly, we find that laforin displays robust phosphatase activity against a phosphorylated complex carbohydrate. Furthermore, this activity is unique to laforin, since several other phosphatases are unable to dephosphorylate polysaccharides. Finally, fusing the carbohydrate-binding module of laforin to the dual specific phosphatase VHR does not result in the ability of this phosphatase to dephosphorylate polysaccharides. Therefore, we hypothesize that laforin is unique in its ability to utilize a phosphorylated complex carbohydrate as a substrate and that this function may be necessary for the maintenance of normal cellular glycogen.