Skeletal muscle (SKM) differentiation is a highly regulated process leading to the formation of specialised cells with reorganised compartments and organelles, such as those of the early secretory pathway. During SKM differentiation the Golgi complex (GC) redistributes close to the nuclear envelope and in small distinct peripheral structures distributed throughout the myotube. Concurrently, GC elements closely associate with endoplasmic
reticulum-exit sites (ERES). The mechanisms underlying this reorganisation and its relevance for SKM differentiation are poorly understood. Here, we show, by time-lapse imaging studies, that the changes in GC organisation involve GC fragmentation and redistribution of ERES with the formation of tightly associated GC–ERES units. We show that knockdown of p115 (also known as USO1) or GM130(also known asGOLGA2), two regulators of the early secretory pathway, impairs GC and ERES reorganisation. This in turn results in inhibition of myotube fusion and M-cadherin transport to the sarcolemma. Taken together, our data suggest that the correct reorganisation of the early secretory pathway components plays an important role in SKMdifferentiation and, thus, associated pathologies.
