Dysferlin mediates membrane tubulation and links T-tubule biogenesis to muscular dystrophy - PubMed (original) (raw)

. 2017 Mar 1;130(5):841-852.

doi: 10.1242/jcs.198861. Epub 2017 Jan 19.

Affiliations

• PMID: 28104817
• DOI: 10.1242/jcs.198861

Dysferlin mediates membrane tubulation and links T-tubule biogenesis to muscular dystrophy

Julia Hofhuis et al. J Cell Sci. 2017.

Abstract

The multi-C2 domain protein dysferlin localizes to the plasma membrane and the T-tubule system in skeletal muscle; however, its physiological mode of action is unknown. Mutations in the DYSF gene lead to autosomal recessive limb-girdle muscular dystrophy type 2B and Miyoshi myopathy. Here, we show that dysferlin has membrane tubulating capacity and that it shapes the T-tubule system. Dysferlin tubulates liposomes, generates a T-tubule-like membrane system in non-muscle cells, and links the recruitment of phosphatidylinositol 4,5-bisphosphate to the biogenesis of the T-tubule system. Pathogenic mutant forms interfere with all of these functions, indicating that muscular wasting and dystrophy are caused by the dysferlin mutants' inability to form a functional T-tubule membrane system.

Keywords: 5-bisphosphate; C2 domain protein; Dysferlin; Dysferlinopathy; Limb-girdle muscular dystrophy type 2B; Miyoshi myopathy; Muscular dystrophy; Phosphatidylinositol 4; T-tubule system.

© 2017. Published by The Company of Biologists Ltd.

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