神经退行性变
自噬
神经科学
化学
计算生物学
生物
医学
生物化学
疾病
病理
细胞凋亡
作者
H. Yamaguchi,Shinya Honda,Satoru Torii,Kimiko Shimizu,K. Katoh,Keisuke Miyake,Noriko Miyake,Nobuhiro Fujikake,Hajime Tajima Sakurai,Satoko Arakawa,Shigeomi Shimizu
标识
DOI:10.1038/s41467-020-18892-w
摘要
Abstract Alternative autophagy is an Atg5/Atg7-independent type of autophagy that contributes to various physiological events. We here identify Wipi3 as a molecule essential for alternative autophagy, but which plays minor roles in canonical autophagy. Wipi3 binds to Golgi membranes and is required for the generation of isolation membranes. We establish neuron-specific Wipi3-deficient mice, which show behavioral defects, mainly as a result of cerebellar neuronal loss. The accumulation of iron and ceruloplasmin is also found in the neuronal cells. These abnormalities are suppressed by the expression of Dram1, which is another crucial molecule for alternative autophagy. Although Atg7 - deficient mice show similar phenotypes to Wipi3-deficient mice, electron microscopic analysis shows that they have completely different subcellular morphologies, including the morphology of organelles. Furthermore, most Atg7/Wipi3 double-deficient mice are embryonic lethal, indicating that Wipi3 functions to maintain neuronal cells via mechanisms different from those of canonical autophagy.
科研通智能强力驱动
Strongly Powered by AbleSci AI