ESCRTs Cooperate with a Selective Autophagy Receptor to Mediate Vacuolar Targeting of Soluble Cargos

作者：Liu Xiao Man; Sun Ling Ling; Hu Wen; Ding Yue He; Dong Meng Qiu; Du Li Lin^*

来源：Molecular Cell, 2015, 59(6): 1035-1042.

DOI：10.1016/j.molcel.2015.07.034

Autophagy transports cytosolic materials into lysosomes/vacuoles either in bulk or selectively. Selective autophagy requires cargo receptor proteins, which usually link cargos to the macroautophagy machinery composed of core autophagy-related (Atg) proteins. Here, we show that fission yeast Nbr1, a homolog of mammalian autophagy receptor NBR1, interacts with and facilitates the transport of two cytosolic hydrolases into vacuoles, in a way reminiscent of the budding yeast cytoplasm-to-vacuole targeting (Cvt) pathway, a prototype of selective autophagy. We term this pathway Nbr1-mediated vacuolar targeting (NVT). Surprisingly, unlike the Cvt pathway, the NVT pathway does not require core Atg proteins. Instead, it depends on the endosomal sorting complexes required for transport (ESCRTs). NVT components colocalize with ESCRTs at multivesicular bodies (MVBs) and rely on ubiquitination for their transport. Our findings demonstrate the ability of ESCRTs to mediate highly selective autophagy of soluble cargos, and suggest an unexpected mechanistic versatility of autophagy receptors.

• 出版日期2015-9-17
• 单位北京师范大学; 北京生命科学研究所