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Role of the protein dystroglycan's end sequence in muscle cell function revealed

01 April 2023

LARGE Links

Every muscle fibre in your body is packed with muscle cells firmly attached to a surrounding sheet called the basement membrane. This attachment requires a protein on muscle cells called dystroglycan and the help of the enzyme LARGE1. LARGE1 makes another protein, matriglycan, directly onto dystroglycan's outward-pointing end, forming a bridge to the basement membrane. Interfere with dystroglycan and the disease muscular dystrophy occurs. Researchers dig deeper using mice genetically engineered with dystroglycan lacking its outward-pointing stretch. Measuring specific protein levels, they find now LARGE1 can only make stunted forms of matriglycan in muscle cells. Dystroglycan could nonetheless bind the basement membrane but the muscle couldn't work properly. Fluorescent microscopy revealed disrupted neuromuscular junctions (pictured, bottom) – connections between a muscle (green) and its nerves (red) – compared with normal mice (top). This helps unpick dystroglycan’s role in muscle diseases.

Written by Lux Fatimathas

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