Gyp1透過改變內膜運輸機制調控自噬作用之進程

Abstract

自噬作用為一個對維持細胞內物質恆定非常重要的自分解過程，其可協助細胞應對細胞內部養分的缺乏和細胞外部的環境壓力。自噬作用進行時，一部份的胞質由雙層膜構造的自噬體包裹，並與濾泡結合進而分解。很多蛋白質及其複合體參與其過程。前人研究發現內膜運輸機制亦參與調控自噬作用。Ypt/Rab GTP酶蛋白家族 (Ypt/Rab GTPase protein family) 為其中一個調控內膜運輸機制的重要蛋白質複合物。其中Ypt1和Ypt7均參與自噬作用的調控，Ypt1可調控自噬作用起始過程中的Atg1/Atg13複合物之生成，而Ypt7則為自噬體與濾泡結合的必需因子。Ypt/Rab GTP酶蛋白家族的活性由鳥苷酸轉換因子 (guanine-nucleotide exchange factors) 及GTP酶活化蛋白 (GTPase activation proteins) 調節。其中GTP酶活化蛋白Gyp1被認為是細胞中調控Ypt1及Ypt7的重要蛋白。本研究中，我們發現缺乏Gyp1的細胞會出現自噬作用缺陷，且當細胞缺乏Gyp1時，內膜運輸機制會失衡。

Autophagy is a self-degradation process that is important to sustain cell homeostasis responding to nutrient stresses and extracellular signals. During autophagy, a part of cytoplasm is engulfed by double-membrane autophagosomes, which fuse with the vacuole for degradation. Many protein complexes are involved. Several researches have proved that membrane trafficking pathway is involved in autophagy regulation. The Ypt/Rab GTPase protein family is one of the important protein complex regulating membrane trafficking. Previous studies have shown that Ypt1 and Ypt7 could both regulate autophagy process. Ypt1 regulates the formation of Atg1/Atg13 complex, a requirement of autophagy induction. On the other hand, Ypt7 is the essential factor for fusion between autophagosomes and the vacuole. Activity of Ypt/Rab GTPase proteins are modulated by guanine-nucleotide exchange factors (GEFs) and GTPase activation proteins (GAPs). Gyp1 is the GAP protein of Ypt1 and Ypt7 in yeast. In my study, gyp1D cells showed bulk autophagy and Cvt pathway defect. gyp1D cells also had conventional membrane trafficking defect phenotype.