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Mol Biol Cell. 2019 Jan 2:mbcE18110718. doi: 10.1091/mbc.E18-11-0718. [Epub ahead of print]

Clathrin plaques and associated actin anchor intermediate filaments in skeletal muscle.

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Sorbonne Université, INSERM, Institute of Myology, Centre of Research in Myology, UMRS 974, F-75013, Paris, France.
Department of Physiology, Sorbonne Université, UPMC Univ Paris 06, Pitié-Salpêtrière Hospital, Paris, France.
Institut de Biologie Paris-Seine, Sorbonne Université, UPMC Univ Paris 06, CNRS, FR3631, Paris, France.
Neuromuscular Morphology Unit, Institute of Myology, Pitié-Salpêtrière Hospital, Paris, France.
INSERM UMRS_1166, Sorbonne Université, UPMC Univ Paris 06, Institute of Cardiometabolism and Nutrition, Paris, France.


Clathrin plaques are stable features of the plasma membrane observed in several cell types. They are abundant in muscle, where they localize at costameres which link the contractile apparatus to the sarcolemma and connect the sarcolemma to the basal lamina. Here, we show that clathrin plaques and surrounding branched actin filaments form microdomains which anchor a three-dimensional desmin intermediate filament web. Depletion of clathrin plaque and branched actin components causes accumulation of desmin tangles in the cytoplasm. We show that dynamin 2 whose mutations cause centronuclear myopathy (CNM), regulates both clathrin plaques and surrounding branched actin filaments while CNM-causing mutations lead to desmin disorganization in a CNM mouse model and patient biopsies. Our results suggest a novel paradigm in cell biology, where clathrin plaques act as platforms capable of recruiting branched cortical actin which in turn anchor intermediate filaments, both essential for striated muscle formation and function. Movie S1 Movie S1 Clathrin structures on the surface of myotubes anchor intermediate filaments. Platinum replica EM imaging with electron tomography was achieved by collecting images at different tilt angles up to ±25° relative to the plane of the sample. Clathrin lattices are pseudocolored in purple, branched actin in orange and intermediate filaments in red.


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