The SNARE proteins are involved in a diverse set of cellular processes, mainly responsible for helping vesicle trafficking between membranes. They have specificity and undergo numerous modifications after transcription that might aid in regulating their function. The SNARE Ykt6 protein, specifically, deals with vesicle trafficking. It is highly conserved in all eukaryotes. It was initially found in yeast and has been found to be involved with the trafficking of membrane vesicles both inside and outside the Golgi apparatus. It cycles between the cytosol and membrane-bound compartments. The protein also plays a role in mammals involving secretory pathways, endocytic pathways, and macroautophagy pathways.
In the paper, A conformational switch driven by phosphorylation regulates the activity of the evolutionary conserved SNARE Ykt6, by Dr. Takahashi et al., they investigated the SNARE ykt6 protein and its regulation. Using a multidisciplinary approach, they found that the phosphorylation of Ykt6, regulated by Ca+2 concentrations, induced a conformational change, allowing Ykt6 to switch from a closed cytosolic form to an open membrane-bound form. Additionally, they found that this phosphorylation is regulated by protein kinase C iota type and is sensitive to calcineurin, which is a key determinant of binding affinity and specificity for protein interactions. When Ykt6 is in its phosphorylated form, there is a high affinity to its binding partners. Then they examined Ykt6 in its open conformation and how it can impact secretary and autophagy pathways, which are both pathways a part of the vesicular transport pathway. They found that in the secretory pathway, when the Ytk6 protein is in its open phosphorylated form (mutant) it can lead to defects and blocks in the pathway. Then for the autophagy pathway, they discovered that Ykt6 mutant blocked autophagic flux and that the phosphorylation of Ykt6 plays a key inhibitory role in the early steps of autophagy. Lastly, the researchers approached SNARE Ykt6 using a Parkinson’s disease model. They found that defects in Ca+2 homeostasis secretory pathway, autophagy pathway have been implicated with Parkinson’s disease. Using in vivo studies in C. elegans, they found that dopaminergic neurons are sensitive to Ykt6 dosage and its phosphorylated state. Ykt6’s regulation is highly important because it is crucial to achieve the right equilibrium in the Ykt6 phosphorylation state to reach proper function. If its equilibrium shifts it can affect the secretory pathway and autophagy pathway negatively. The findings from this study reveal SNARE Ytk6’s regulation and activity and provide insight into Parkinson’s which aids therapeutic effects for this neurodegenerative disease.
In the paper, A pan-cancer analysis of the oncogenic role of YKT6 in human tumors, by Dr. Zhang et al., they explore the association between molecular mechanisms and clinical prognosis. They utilized the Cancer Genome Atlas and Gene Expression Omnibus database to gather genomics data about various types of tumors, which enabled them to conduct pan-cancer analyses. They used an online tool called TIMER2 to collect data about the association between Ykt6 level and immune filtration. They used this tool to analyze the expression of Ykt6 between tumor tissues and normal tissues. They found that the expression of Ykt6 was significantly overexpressed in numerous cancers such as breast invasive carcinoma, lung adenocarcinoma, colon adenocarcinoma, stomach adenocarcinoma, and more. However, the expression of Ykt6 was significantly downregulated in kidney renal clear carcinoma and thyroid carcinoma. Then, they used GEPIA2, an online tool, to measure the expression of Ykt6 in different tumor stages. They discovered that there was a high correlation between the level of Ykt6 and the pathological stage of tumors. Additionally, they investigated the relationship between Ykt6 and the prognosis of patients with various cancers. The groups were separated into either high expression or low expression. They found that high expression of Ykt6 was positively correlated with poor prognosis of overall survival and with poor disease free survival prognosis. Lastly looking at DNA methylation, there was a hypermethylation in the promoter region of Ykt6 in kidney renal clear cell carcinoma, lung squamous cell carcinoma, and pancreatic adenocarcinoma, and a hypomethylation in the promoter region of bladder urothelial carcinoma, head and neck squamous, kidney papillary carcinoma, prostate adenocarcinoma, lung adenocarcinoma. The prevalence and progress of tumors was affected by either upregulation or downregulation of DNA methylation, which influenced the expression of the tumor gene. The difference between tumor tissues and normal tissues, in regards to Ykt6 methylation, revealed that there are distinct results at different methylation results. This analysis of multiple different cancers and various tumor types provides a deeper insight into Ykt6 from a clinical viewpoint.
While both of these articles explore SNARE Ykt6, they examine its implications in different diseases. The first paper focuses more on Ykt6’s molecular mechanisms and how it can affect cell pathways, and then apply it to a Parkinson’s disease model. The second paper focuses more about the clinical aspects of Ytk6 in a pan-cancer analysis. Both papers utilize and understand the mechanisms of Ykt6 and its regulation and then apply it to diseases. It is interesting to see how despite the articles approaching Ykt6 with different disease models, they still examine the same mechanisms of Ykt6. Either the upregulation or downregulation can play a role in the pathobiology of Parkinson's, and it can play a role in cancers as well. It shows that Ykt6 contains complicated mechanisms that can play a vast role in numerous diseases, and this insight can ultimately aid in the therapeutic efforts for these illnesses. These articles play a crucial role in examining Ykt6’s relationships and associations on a molecular level as well as on a clinical viewpoint. Only some of Ykt6’s roles and implications have been investigated and its vast capabilities encourage more research to be conducted on this topic.
References:
McGrath, Kaitlyn et al. “A conformational switch driven by phosphorylation regulates the activity of the evolutionarily conserved SNARE Ykt6.” Proceedings of the National Academy of Sciences of the United States of America vol. 118,12 (2021): e2016730118. doi:10.1073/pnas.2016730118
Zhang, Xuezhong et al. “A pan-cancer analysis of the oncogenic role of YKT6 in human tumors.” Medicine vol. 102,15 (2023): e33546. doi:10.1097/MD.0000000000033546
No comments:
Post a Comment