Fission yeast Nbr1 and ESCRTs mediate Atg-independent selective autophagy of cytosolic hydrolases

来源 :The 7th International Symposium on Autophagy 2015(第七届自噬国际研讨会 | 被引量 : 0次 | 上传用户:mashangdenglu998
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  Autophagy transports cytosolic materials into lysosomes/vacuoles either in bulk or selectively.A prototype of selective autophagy, the budding yeast cytoplasm-to-vacuole targeting (Cvt)pathway, utilizes core autophagy-related (Atg) proteins and the cargo receptor Atg19 to deliver specific hydrolases into vacuoles.Here, we show that fission yeast Nbr1, a homolog of mammalian autophagy receptor NBR1, interacts with two cytosolic hydrolases, Lap2 and Ape2 and facilitates their transport into vacuoles.We term this pathway Nbr1-mediated vacuolar targeting (NVT).Nbr1, Lap2 and Ape2 assemble into one complex in an interdependent manner.The ZZ fingers of Nbr1 are necessary and sufficient for the interactions with Lap2 and Ape2,while both the 77 fingers and the FW domain are required for the vacuolar targeting function.Unexpectedly, the NVT pathway does not require core Atg proteins but depends on the endosomal sorting complexes required for transport (ESCRTs).NVT components co-localize with ESCRTs at endosomes and rely on ubiquitination for their transport.Our findings demonstrate that an autophagy receptor can act independently of the macroautophagy machinery, and reveal the ability of ESCRTs to mediate highly selective autophagy of soluble cargos.
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