The LIR motif - crucial for selective autophagy
The LIR motif - crucial for selective autophagy
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DOI：
10.1242/jcs.126128
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发表时间：
2013-08-01
影响因子：
4
通讯作者：
Johansen, Terje
中科院分区：
文献类型：
--
作者：
Birgisdottir, Asa Birna;Lamark, Trond;Johansen, Terje
（宏观）自噬是对细胞和组织稳态至关重要的大分子和细胞器的基本降解过程。近年来，自噬研究获得了强劲的势头，因为它与癌症，神经退行性疾病，肌肉萎缩症，脂质储存障碍，发育，衰老和先天免疫有关。自噬传统上被认为是一种大量降解过程，在营养饥饿时被动员起来，以补充细胞的构建模块并跟上能量需求。最近，在一系列描述各种形式的选择性自噬的论文之后，这种观点发生了巨大的变化。一个主要的驱动力是发现了特异性的自噬受体，其将货物隔离成形成自噬体（吞噬细胞）。这种选择性的核心在于LC3相互作用区（LIR）基序，它确保自噬受体靶向锚定在吞噬细胞膜上的LC3（或其他ATG8家族蛋白）。含LIR的蛋白质包括货物受体、基础自噬装置的成员、与囊泡及其转运相关的蛋白质、Rab GTP酶激活蛋白（GAP）和通过选择性自噬降解的特异性信号传导蛋白。在这里，我们评论这些新的见解，并专注于含LIR的蛋白质与ATG8蛋白质家族成员的相互作用。
(Macro) autophagy is a fundamental degradation process for macromolecules and organelles of vital importance for cell and tissue homeostasis. Autophagy research has gained a strong momentum in recent years because of its relevance to cancer, neurodegenerative diseases, muscular dystrophy, lipid storage disorders, development, ageing and innate immunity. Autophagy has traditionally been thought of as a bulk degradation process that is mobilized upon nutritional starvation to replenish the cell with building blocks and keep up with the energy demand. This view has recently changed dramatically following an array of papers describing various forms of selective autophagy. A main driving force has been the discovery of specific autophagy receptors that sequester cargo into forming autophagosomes (phagophores). At the heart of this selectivity lies the LC3-interacting region (LIR) motif, which ensures the targeting of autophagy receptors to LC3 (or other ATG8 family proteins) anchored in the phagophore membrane. LIR-containing proteins include cargo receptors, members of the basal autophagy apparatus, proteins associated with vesicles and of their transport, Rab GTPase-activating proteins (GAPs) and specific signaling proteins that are degraded by selective autophagy. Here, we comment on these new insights and focus on the interactions of LIR-containing proteins with members of the ATG8 protein family.