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

Lux Fatimathas

Writer

Having pursued science through a career in research, communications and publishing, she is currently a writer and editor for a healthcare marketing agency and also juggles freelance science writing.

• Image from work by Hidehiko Okuma and colleagues
• Wellstone Muscular Dystrophy Specialized Research Center, Department of Molecular Physiology and Biophysics and Department of Neurology, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, IA, USA
• Image originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)
• Published in eLife, February 2023