The Golgi Apparatus: A Voyage through Time, Structure, Function and Implication in Neurodegenerative Disorders

Abstract

This comprehensive review article dives deep into the Golgi apparatus, an essential organelle in cellular biology. Beginning with its discovery during the 19th century until today's recognition as an important contributor to cell function. We explore its unique organization and structure as well as its roles in protein processing, sorting, and lipid biogenesis, which play key roles in maintaining homeostasis in cellular biology. This article further explores Golgi biogenesis, exploring its intricate processes and dynamics that contribute to its formation and function. One key focus is its role in neurodegenerative diseases like Parkinson's, where changes to the structure or function of the Golgi apparatus may lead to their onset or progression, emphasizing its key importance in neuronal health. At the same time, we examine the intriguing relationship between Golgi stress and endoplasmic reticulum (ER) stress, providing insights into their interplay as two major cellular stress response pathways. Such interdependence provides a greater understanding of cellular reactions to protein misfolding and accumulation, hallmark features of many neurodegenerative diseases. In summary, this review offers an exhaustive examination of the Golgi apparatus, from its historical background to its role in health and disease. Additionally, this examination emphasizes the necessity of further research in this field in order to develop targeted therapeutic approaches for Golgi dysfunction-associated conditions. Furthermore, its exploration is an example of scientific progress while simultaneously offering hope for developing innovative treatments for neurodegenerative disorders.

Keywords: Golgi apparatus; Golgi disfunction; Parkinson’s disease; endoplasmic reticulum stress; neurobiology; neurodegenerative diseases.

Figure 1

Membranes and cargo proteins leave the endoplasmic reticulum (ER), leaving behind transport vesicles packed with proteins by attaching themselves to the COPII coat. This binding involves exit signals on membrane proteins being trapped by the COPII coat and binding with it via their cytosolic tails; some membrane proteins trapped by it then act as cargo receptors to help package other proteins into transport vesicles for transportation. Membrane fusion and the formation of a continuous compartment involve interactions among matching v-SNAREs and t-SNAREs on adjacent identical membranes, beginning with the NSF separation of identical pairs on both membranes displaying matching SNAREs. Thereafter, homotypic fusion expands further by joining with similar-typed vesicles that display matching SNAREs. Once transport vesicles have left an ER exit site and shed their outer layers, they begin merging together. This process, known as homotypic fusion, involves membranes from within one compartment joining forces as opposed to heterotypic fusion, where separate compartments combine; it differs from heterotypic fusion, in which different compartments come together through merging. Like heterotypic fusion, homotypic fusion also requires two corresponding SNAREs, but unlike heterotypic fusion, both membranes contribute v-SNAREs and t-SNAREs, thus creating an even greater level of interaction than heterotypic fusion does.

Figure 2

Signaling pathways play an essential role in organizing the Golgi apparatus and maintaining neuronal polarity during neurogenesis. First, lipid transfer proteins (PITPNA/PITPNB) augment GOLPH3 recruitment to the Golgi apparatus via PI4P signaling; which promotes its positioning towards MYO18A’s target compartment. Secondly, STK25 and Mst4, two downstream effectors of LKB1, possess the capacity to co-immunoprecipitate with STRAD and bind to Golgi matrix protein GM130, acting as key organizers within its organelles. Reelin and Dab1 also regulate the expansion of Golgi bodies into pyramidal neurons’ apical processes. Finally, the BIG2-ARF1-RhoA-mDia1 signaling pathway plays an integral role in controlling dendritic Golgi deployment and growth in newly created hippocampal neurons in adults.

Figure 3

Leucine-rich repeat kinase 2 (LRRK2) acts as a central hub that interacts with numerous molecules, such as Rab family proteins, vacuolar protein sorting protein (VPS), Golgi outposts and Golgi posts (GOPs), cyclin-dependent kinase 5 (CDK5), Ppotein kinase C (PKC), and synapse-associated protein 97 (SAP97), among others. These interactions impact trans-Golgi network membrane transport and Golgi morphology which ultimately contribute to the development of pathological features associated with Parkinson’s disease (PD).