Mutations in the gene encoding the glycogen phosphatase laforin result in the fatal childhood epilepsy Lafora disease (LD). A cellular hallmark of LD is cytoplasmic, hyper-phosphorylated, glycogen-like aggregates called Lafora bodies (LBs) that form in nearly all tissues and drive disease progression. Additional tools are needed to define the cellular function of laforin, understand the pathological role of laforin in LD, and determine the role of glycogen phosphate in glycogen metabolism. We present the generation and characterization of laforin nanobodies. We identify multiple classes of specific laforin-binding nanobodies and determine their binding epitopes using hydrogen deuterium exchange (HDX) mass spectrometry. Further, one family of nanobodies is identified that serves as an inhibitor of laforin catalytic activity. The laforin nanobodies are an important set of tools that open new avenues to define unresolved questions.

中文翻译：

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Laforin纳米抗体的产生与表征

编码糖原磷酸酶laforin的基因中的突变会导致致命的儿童癫痫性Lafora疾病（LD）。LD的细胞标志是称为Lafora体（LB）的细胞质，超磷酸化，糖原样聚集体，几乎在所有组织中形成并推动疾病进展。需要其他工具来定义laforin的细胞功能，了解laforin在LD中的病理作用以及确定糖原磷酸在糖原代谢中的作用。我们介绍了Laforin纳米抗体的生成和表征。我们确定特定的laforin结合纳米抗体的多个类别，并使用氢氘交换（HDX）质谱法确定它们的结合表位。此外，鉴定了一个家族的纳米抗体，其可作为laforin催化活性的抑制剂。