"Skeletal muscle (SKM) cell differentiation and remodeling require synthesis and transport of an enormous amount of proteins to build up its’ highly specialized structures, likely entailing an important involvement of the secretory pathway. The sarcoplasmic reticulum (SR) of SKM cells is a specialized form of endoplasmic reticulum (ER), formed by a complex network of tubules and cisternae sharing a common lumen, that can be subdivided in the junctional SR, responsible for calcium release, and the longitudinal SR, involved in calcium uptake. In SKM cells, the canonical ER distribution is not clear: cells may contain two major rough ER subcompartments, one without exit sites, localized in correspondence to the I-band, and a second responsible for export activity toward the Golgi Complex (GC), near the Z-disc. The GC in terminally differentiated SKM cells is organized in a fiber-type dependent fashion and, formed by very small GC elements consisting in a small stack of cisternae localized around the nuclei and in all the fiber. Interestingly, changes in GC organization in differentiating SKM cells follow pathways common to all mammalian cells. In order to find new insights on secretory pathway mechanisms in SKM differentiation, this project is aimed at answering two questions: 1- How do specialized domains, as SR, ER, GC and vesicles, reciprocally organize during SKM differentiation?; 2- What is the impact of the down regulation of proteins of the secretory pathway on differentiation and on specialized domains assembly in SKM cells?This project will be developed by exploiting the Researcher experience in the field of SKM differentiation and, the host group high-standard knowledge of the state of the art microscopy approaches and of vesicle trafficking field. Potentially the programme will improve the approaches available to study SKM differentiation and, will provide opportunities to reveal biological processes that will be very important for the scientific community"