title: ESCRTs Cooperate with a Selective Autophagy Receptor to Mediate Vacuolar Targeting of Soluble Cargos.
abstract: 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.
authors.affiliation: College of Life Sciences, Beijing Normal University, Beijing 100875, China; National Institute of Biological Sciences, Collaborative Innovation Center for Cancer Medicine, Beijing, 102206, China.
authors.forename: Xiao-Man
authors.initials: XM
authors.lastname: Liu
authors.affiliation: National Institute of Biological Sciences, Collaborative Innovation Center for Cancer Medicine, Beijing, 102206, China.
authors.forename: Ling-Ling
authors.initials: LL
authors.lastname: Sun
authors.affiliation: National Institute of Biological Sciences, Collaborative Innovation Center for Cancer Medicine, Beijing, 102206, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Hu
authors.affiliation: National Institute of Biological Sciences, Beijing 102206, China.
authors.forename: Yue-He
authors.initials: YH
authors.lastname: Ding
authors.affiliation: National Institute of Biological Sciences, Beijing 102206, China.
authors.forename: Meng-Qiu
authors.initials: MQ
authors.lastname: Dong
authors.affiliation: National Institute of Biological Sciences, Collaborative Innovation Center for Cancer Medicine, Beijing, 102206, China. Electronic address: dulilin@nibs.ac.cn.
authors.forename: Li-Lin
authors.initials: LL
authors.lastname: Du
mesh_terms: D000626:Aminopeptidases / Q000378:metabolism; D001343:Autophagy; D000071183:Autophagy-Related Proteins; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D056827:Endosomal Sorting Complexes Required for Transport / Q000502:physiology*; D021381:Protein Transport; D012568:Schizosaccharomyces / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism*; D012995:Solubility; D014157:Transcription Factors / Q000378:metabolism*; D054875:Ubiquitination; D014617:Vacuoles / Q000378:metabolism*
chemical_list: D000071183:Autophagy-Related Proteins; D002868:Chromosomal Proteins, Non-Histone; D056827:Endosomal Sorting Complexes Required for Transport; D029702:Schizosaccharomyces pombe Proteins; D014157:Transcription Factors; C513475:atg11 protein, S pombe; D000626:Aminopeptidases