ZZ domains keep cytosol to vacuole delivery whiZZing along

Abstract

Selective autophagy relies on adaptor proteins to bind and transport cargos (or substrates) to the lysosome or vacuole, yet the mechanisms for cargo recognition are not well understood. In this issue, Wang et al (2021) showed that in the fission yeast, Nbr1, a homolog of a mammalian selective autophagy adaptor, recognizes vacuolar hydrolases Ams1 and Ape4 through both versatile and cargo‐specific interactions with the Nbr1 ZZ1 domain.

NBR1: The archetypal selective autophagy receptor

“…Lap2 and Ape2 bind to ZZ2 and ZZ3. Surprisingly, this Nbr1-mediated vacuolar targeting (NVT) pathway in S. pombe is not mediated by autophagy components but by endosomal-sorting complexes required for transport (ESCRTs) in a process similar to microautophagy ( Hama et al, 2021 ; Wang et al, 2021 ). Interestingly, the ZZ domain of mammalian p62, but not that of mammalian NBR1, is also used for cargo recognition by binding to N-arginylated proteins ( Cha-Molstad et al, 2017 ).…”