逆转体
内体
细胞生物学
生物
自噬
转运蛋白
内吞作用
mTORC1型
PI3K/AKT/mTOR通路
生物化学
受体
信号转导
细胞内
细胞凋亡
作者
Julian M. Carosi,Leanne K. Hein,Jarrod J. Sandow,L. Dang,Kathryn J. Hattersley,Donna Denton,Sharad Kumar,Timothy J. Sargeant
出处
期刊:Autophagy
[Informa]
日期:2023-11-17
卷期号:20 (4): 863-882
被引量:1
标识
DOI:10.1080/15548627.2023.2281126
摘要
Retromer prevents the destruction of numerous receptors by recycling them from endosomes to the trans-Golgi network or plasma membrane. This enables retromer to fine-tune the activity of many signaling pathways in parallel. However, the mechanism(s) by which retromer function adapts to environmental fluctuations such as nutrient withdrawal and how this affects the fate of its cargoes remains incompletely understood. Here, we reveal that macroautophagy/autophagy inhibition by MTORC1 controls the abundance of retromer+ endosomes under nutrient-replete conditions. Autophagy activation by chemical inhibition of MTOR or nutrient withdrawal does not affect retromer assembly or its interaction with the RAB7 GAP protein TBC1D5, but rather targets these endosomes for bulk destruction following their capture by phagophores. This process appears to be distinct from amphisome formation. TBC1D5 and its ability to bind to retromer, but not its C-terminal LC3-interacting region (LIR) or nutrient-regulated dephosphorylation, is critical for retromer to be captured by autophagosomes following MTOR inhibition. Consequently, endosomal recycling of its cargoes to the plasma membrane and trans-Golgi network is impaired, leading to their lysosomal turnover. These findings demonstrate a mechanistic link connecting nutrient abundance to receptor homeostasis.
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