LC3B is indispensable for selective autophagy of p62 but not basal autophagy

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• 作者：Yoko Maruyama^a ; ^b ; Yu-Shin Sou^a ; Shun Kageyama^a ; Takao Takahashi^b ; Takashi Ueno^c ; Keiji Tanaka^d ; Masaaki Komatsu^a ; ^e ; ^{komatsu-ms@igakuken.or.jp" class="auth_mail} ; Yoshinobu Ichimura^a ; ^{ichimura-ys@igakuken.or.jp" class="auth_mail}
• 关键词：GABARAP ; gamma-aminobutyrate receptor-associated protein ; GEC-1 ; glandularepithelial cell protein 1 ; GATE-16 ; golgi-associated ATPase enhancer of 16  ; kDa ; ITC ; isothermal titration calorimetry ; LC3 ; microtubule-associated protein 1 light chain 3/MAP1LC3 ; LIR ; LC3-interacting region ; PE ; phosphatidylethanolamine
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：28 March, 2014
• 年：2014
• 卷：446
• 期：1
• 页码：309-315
• 全文大小：1299 K

文摘

Autophagy is a unique intracellular protein degradation system accompanied by autophagosome formation. Besides its important role through bulk degradation in supplying nutrients, this system has an ability to degrade certain proteins, organelles, and invading bacteria selectively to maintain cellular homeostasis. In yeasts, Atg8p plays key roles in both autophagosome formation and selective autophagy based on its membrane fusion property and interaction with autophagy adaptors/specific substrates. In contrast to the single Atg8p in yeast, mammals have 6 homologs of Atg8p comprising LC3 and GABARAP families. However, it is not clear these two families have different or similar functions. The aim of this study was to determine the separate roles of LC3 and GABARAP families in basal/constitutive and/or selective autophagy. While the combined knockdown of LC3 and GABARAP families caused a defect in long-lived protein degradation through lysosomes, knockdown of each had no effect on the degradation. Meanwhile, knockdown of LC3B but not GABARAPs resulted in significant accumulation of p62/Sqstm1, one of the selective substrate for autophagy. Our results suggest that while mammalian Atg8 homologs are functionally redundant with regard to autophagosome formation, selective autophagy is regulated by specific Atg8 homologs.