Dysferlin regulates cell membrane repair by facilitating injury-triggered acid sphingomyelinase secretion

• DOI: 10.1038/cddis.2014.272
• Publication Date: 2014-06-26T13:13:24Z
• Authors: A Defour; J H Van der Meulen; R Bhat; A Bigot; R Bashir; K Nagaraju; J K Jaiswal
• Keywords: Dysferlin; Acid sphingomyelinase; LAMP1; Sarcolemma

Dysferlin deficiency compromises the repair of injured muscle, but underlying cellular mechanism remains elusive. To study this phenomenon, we have developed mouse and human myoblast models for dysferlinopathy. These dysferlinopathic myoblasts undergo normal differentiation a deficit in their ability to focal injury cell membrane. Imaging cells undergoing showed that dysferlin-deficit decreased number lysosomes present at membrane, resulting delay reduction injury-triggered lysosomal exocytosis. We find does not involve formation intracellular membrane patch through lysosome–lysosome fusion; instead, individual fuse with releasing acid sphingomyelinase (ASM). ASM secretion was reduced cells, acute treatment restored myofibers. Our results provide dysferlin-mediated skeletal muscle sarcolemma identify as potential therapy