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.

Bi‐allelic loss of function variants in GOLGA2 are associated with a complex neurological phenotype: Report of a second family

“…Golgins are a family of Coiled-coil proteins associated with the Golgi apparatus and are necessary for tethering events in the membrane fusion and structural support for Golgi cisternae during vesicular trafficking. 14 The proband exhibited neurological and skeletal muscle abnormalities that are similar to the previously reported single case of the GOLGA2 mutation in a family. 6 GOLGA2 is a key regulator of the neuromuscular system.…”

The GTPase Arf1 Is a Determinant of Yeast Vps13 Localization to the Golgi Apparatus

“…In conclusion, finding the interactions between Arf1 GTPase, Vps13, and the PH-like domain of VPS13A is important for a better understanding of the pathogenesis of diseases caused by mutations in VPS13 genes. The Golgi is a central hub for protein sorting, which is important for neurodevelopment and for secretion of neurotransmitters, and its dysfunction is linked to several neurodegenerative disorders [38,40,41]. ARF1 gene mutations are linked to autosomal dominant periventricular nodular heterotopia, a disorder characterized by delayed psychomotor development [78].…”

“…The Arf proteins perform their function through interaction with, and regulation of the activity of, several effector proteins that often possess PH domains responsible for Arf1 binding [36,37]. An increasing number of reports link changes in Golgi morphology to neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis [38,39], but also to many other diseases [40,41]. There are also new studies showing the functional connections between the Golgi and mitochondria [42].…”

OM‐MSCs Alleviate the Golgi Apparatus Stress Response following Cerebral Ischemia/Reperfusion Injury via the PEDF‐PI3K/Akt/mTOR Signaling Pathway

“…It is well documented that GA dysfunction has been implicated in a wide range of human diseases [ 28 ], and the role of GA in oxidative stress-related damage has been studied extensively [ 5 , 29 ]. Previous evidence suggests that oxidative stress caused by cerebral IRI contributes to the upregulation of GOLPH3, GA fragmentation, and intracellular Ca 2+ concentration along with the downregulation of SPCA1, which is referred to as the GA stress response.…”