Golgi Complex form and Function: A Potential Hub Role Also in Skeletal Muscle Pathologies?

• Published in: International journal of molecular sciences Vol. 23; no. 23; p. 14989
• Main Authors: Toniolo, Luana, Sirago, Giuseppe, Fiotti, Nicola, Giacomello, Emiliana
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 30.11.2022; MDPI
• Subjects: Cytology; dystrophin associated protein complex; early secretory pathway; Endoplasmic reticulum; Glycosylation; Golgi apparatus; Golgi Apparatus - metabolism; Golgi Complex; Guanylate cyclase; Humans; Limb girdle muscular dystrophy; Localization; Morphology; Muscle Fibers, Skeletal - metabolism; Muscle, Skeletal - metabolism; Muscles; Muscular Dystrophies - metabolism; Muscular Dystrophies, Limb-Girdle - metabolism; muscular dystrophy; Musculoskeletal system; Mutation; Pathogenesis; Physiology; Plasma; Protein transport; Proteins; Skeletal muscle; Therapeutic targets; Limb girdle muscular dystrophy; glycosylation; muscular dystrophy; Golgi Complex; dystrophin associated protein complex; early secretory pathway
• DOI: 10.3390/ijms232314989
• ISSN: 1422-0067; 1661-6596

A growing number of disorders has been associated with mutations in the components of the vesicular transport machinery. The early secretory pathway consists of Endoplasmic Reticulum, numerous vesicles, and the Golgi Complex (GC), which work together to modify and package proteins to deliver them to their destination. The GC is a hub organelle, crucial for organization of the other secretory pathway components. As a consequence, GC's form and function are key players in the pathogenesis of several disorders. Skeletal muscle (SKM) damage can be caused by defective protein modifications and traffic, as observed in some Limb girdle muscular dystrophies. Interestingly, in turn, muscle damage in Duchenne dystrophic SKM cells also includes the alteration of GC morphology. Based on the correlation between GC's form and function described in non-muscle diseases, we suggest a key role for this hub organelle also in the onset and progression of some SKM disorders. An altered GC could affect the secretory pathway via primary (e.g., mutation of a glycosylation enzyme), or secondary mechanisms (e.g., GC mis-localization in Duchenne muscles), which converge in SKM cell failure. This evidence induces considering the secretory pathway as a potential therapeutic target in the treatment of muscular dystrophies.