The incredible ULKs.
The incredible ULKs.
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DOI：
10.1186/1478-811x-10-7
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发表时间：
2012-03-13
期刊：
影响因子：
--
通讯作者：
Stork B
中科院分区：
文献类型：
--
作者：
Alers S;Löffler AS;Wesselborg S;Stork B
大自噬（Macroautophagy）（通常缩写为自噬）是真核细胞中介导胞内组分的溶酶体降解的进化保守的溶酶体指导的囊泡运输途径。细胞质货物最初被一个特殊的双膜囊泡包围，称为自噬体。通过这种方式，自噬可以帮助去除受损的细胞器，长寿命的蛋白质和蛋白质聚集体，或者作为分子构建块的回收机制。自噬曾经被单细胞生物发明，以补偿波动的外部营养供应。在高等真核生物中，它在各种胁迫条件下强烈增强，例如营养和生长因子剥夺或DNA损伤。丝氨酸/苏氨酸激酶Atg 1是第一个在酵母中鉴定的自噬相关基因（ATG）产物。然而，相应的线虫同源物E11 -51具有额外的神经元功能。脊椎动物基因组最终编码五种密切相关的激酶，其中ULK-51样激酶1（Ulk 1）和Ulk 2都参与调节自噬和进一步的神经元特异性囊泡运输过程。本文主要介绍了脊椎动物Ulk 1/2-Atg 13-FIP 200蛋白复合物在自噬启动中的功能、其从酵母Atg 1-Atg 13-Atg 17复合物的进化过程以及其组分的其他非自噬功能。由于快速的营养和压力依赖的细胞反应主要是由丝氨酸/苏氨酸磷酸化介导的，它将总结我们目前的知识有关的上游信号通路和改变磷酸化状态在这个复杂的自噬诱导。
Macroautophagy (commonly abbreviated as autophagy) is an evolutionary conserved lysosome-directed vesicular trafficking pathway in eukaryotic cells that mediates the lysosomal degradation of intracellular components. The cytoplasmic cargo is initially enclosed by a specific double membrane vesicle, termed the autophagosome. By this means, autophagy either helps to remove damaged organelles, long-lived proteins and protein aggregates, or serves as a recycling mechanism for molecular building blocks. Autophagy was once invented by unicellular organisms to compensate the fluctuating external supply of nutrients. In higher eukaryotes, it is strongly enhanced under various stress conditions, such as nutrient and growth factor deprivation or DNA damage. The serine/threonine kinase Atg1 was the first identified autophagy-related gene (ATG) product in yeast. The corresponding nematode homolog UNC-51, however, has additional neuronal functions. Vertebrate genomes finally encode five closely related kinases, of which UNC-51-like kinase 1 (Ulk1) and Ulk2 are both involved in the regulation of autophagy and further neuron-specific vesicular trafficking processes. This review will mainly focus on the vertebrate Ulk1/2-Atg13-FIP200 protein complex, its function in autophagy initiation, its evolutionary descent from the yeast Atg1-Atg13-Atg17 complex, as well as the additional non-autophagic functions of its components. Since the rapid nutrient- and stress-dependent cellular responses are mainly mediated by serine/threonine phosphorylation, it will summarize our current knowledge about the relevant upstream signaling pathways and the altering phosphorylation status within this complex during autophagy induction.