The role of Gyp1 in autophagy regulation

• Main Authors: Ting-Jung Chang, 張庭榮
• Other Authors: Wei-Pang Huang
• Format: Others
• Language: en_US
• Published: 2016
• Online Access: http://ndltd.ncl.edu.tw/handle/28862576454083908822

碩士 === 國立臺灣大學 === 生命科學系 === 104 === Autophagy is a highly conserved catabolism pathway responding to nutrient starvation, stresses, and extracellular signals. It is a precisely regulated process, which defect is related to many human diseases. In order to cope with different cellular stresses, cells could elicit different types of autophagy, including nonselective autophagy and selective autophagy. Many protein complexes are involved in executing these different types of autophagy. Among them, Atg1 is recruited to the PAS at the early stage of autophagy and forms the basic scaffold structure for autophagosome formation. After the formation of autophagosomes, the completed autophagic vesicles fuse with the vacuole and complete the whole pathway. In addition to the core autophagy regulatory proteins, there are other important factors indispensable for autophagy execution. In the whole autophagy process, the formation of autophagosome would rely heavily on membrane trafficking. Membrane trafficking is an essential process in cell physiology, and is regulated by Rab/Ypt protein family. The Rab/Ypt proteins are GTPases whose activities are modulated by GTPase activation proteins (GAPs) and Guanine nucleotide exchange factors (GEFs). In yeast, Ypt1 and Ypt7, which are Rab/Ypt proteins known to mediate the early and late autophagy process, respectively. In this study, I found that deletion of GYP1, which is a GAP protein of Ypt1 and Ypt7 in yeast, would cause autophagy defect. The autophagy defect of gyp1∆ cells is conserved among different yeast strains and is correlated to viability decrease of the mutant cells under nitrogen starvation stress. Deletion of GYP1 would further cause minor Cvt pathway defect and moderate pexophagy defect. Although I could not observe any change of Atg protein modification in gyp1∆ cells comparing to wild type cells, higher percentages of gyp1∆ cells do show Atg1 puncta at the PAS. I suppose that deletion of GYP1 would disrupt the dynamic balance of membrane trafficking and delay the membrane supply for autophagosomes formation. In conclusion, our results indicated that Gyp1 is required for the control of normal Atg1 recycling, indicating the importance of maintaining the dynamic movement of the endomembrane system in autophagy regulation.