The role of the Golgi apparatus in disease (Review)

Abstract

The Golgi apparatus is known to underpin many important cellular homeostatic functions, including trafficking, sorting and modifications of proteins or lipids. These functions are dysregulated in neurodegenerative diseases, cancer, infectious diseases and cardiovascular diseases, and the number of disease‑related genes associated with Golgi apparatus is on the increase. Recently, many studies have suggested that the mutations in the genes encoding Golgi resident proteins can trigger the occurrence of diseases. By summarizing the pathogenesis of these genetic diseases, it was found that most of these diseases have defects in membrane trafficking. Such defects typically result in mislocalization of proteins, impaired glycosylation of proteins, and the accumulation of undegraded proteins. In the present review, we aim to understand the patterns of mutations in the genes encoding Golgi resident proteins and decipher the interplay between Golgi resident proteins and membrane trafficking pathway in cells. Furthermore, the detection of Golgi resident protein in human serum samples has the potential to be used as a diagnostic tool for diseases, and its central role in membrane trafficking pathways provides possible targets for disease therapy. Thus, we also introduced the clinical value of Golgi apparatus in the present review.

Keywords: Golgi apparatus; Golgi dysfunction; Golgi resident protein; disease; diagnosis; therapy.

Figure 1

Disorders relating to Golgi dysfunction. Disorders relating to Golgi apparatus dysfunction are grouped according to the main tissues/organs affected.

Figure 2

Golgi resident proteins and membrane trafficking pathway. The main membrane trafficking pathways are included. Newly synthesized proteins enter the ER and are sorted into budding vesicles that are dependent on the COPII. Vesicles move to the ERGIC and forward to the CGN and the trans-Golgi cisternae. Finally, vesicles reach the TGN and cargos sort to their final destinations such as lysosomes, endosomes or the plasma membrane. Different mutation in Golgi resident proteins affect different membrane trafficking pathway: i) GM130, Giantin, Fukutin, Dymeclin and SCYL1BP1 (involving anterograde trafficking); ii) COGs (involving retrograde trafficking); iii) TRAPPC2 and GMAP-210 (involving ER to ERGIC); iv) FGD1, ATP2C1 and ARFGEF2 (involving TGN to plasma membrane); and v) COGs, DENND5A and BICD (involving endosome to TGN).