Golgi Structure and Function in Health, Stress, and Diseases

Abstract

The Golgi apparatus is a central intracellular membrane-bound organelle with key functions in trafficking, processing, and sorting of newly synthesized membrane and secretory proteins and lipids. To best perform these functions, Golgi membranes form a unique stacked structure. The Golgi structure is dynamic but tightly regulated; it undergoes rapid disassembly and reassembly during the cell cycle of mammalian cells and is disrupted under certain stress and pathological conditions. In the past decade, significant amount of effort has been made to reveal the molecular mechanisms that regulate the Golgi membrane architecture and function. Here we review the major discoveries in the mechanisms of Golgi structure formation, regulation, and alteration in relation to its functions in physiological and pathological conditions to further our understanding of Golgi structure and function in health and diseases.

Fig. 19.1

Structure, modification, and binding sites on GRASP65 (a) and GRASP55 (b). Rat GRASP65 and GRASP55 sequences are used for illustration. Both GRASPs share a similar structure: a conserved N-terminal GRASP domain consisting of two PDZ domains (PDZ1 and PDZ2) and a C-terminal Serine/Proline-Rich (SPR) domain with multiple phosphorylation sites (indicated by asterisks) that are involved in GRASP modulation during the cell cycle. Both GRASP65 and GRASP55 are peripheral membrane proteins attached to the Golgi membranes via N-terminal myristoylation and the interaction with their membrane-bound partner proteins (GM130 and Golgin-45, respectively). GRASP65-binding proteins Mena and DjA1 have been identified to enhance Golgi ribbon linking and stacking, respectively. GRASP55 is regulated by O-GlcNAcylation depending on the glucose level and interacts with LC3 and LAMP2 to facilitate glucose starvation-induced autophagy