RT Journal Article
SR Electronic
T1 ESCRT-Independent Surface Receptor And Transporter Protein Degradation By The ILF Pathway
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 167411
DO 10.1101/167411
A1 McNally, Erin Kate
A1 Brett, Christopher Leonard
YR 2017
UL http://biorxiv.org/content/early/2017/07/22/167411.abstract
AB Surface receptor and transporter protein down-regulation drives cell signaling, quality control and metabolism underlying diverse physiology. After endocytosis, proteins are delivered to endosomes where ESCRTs package them into intralumenal vesicles, which are degraded by acid hydrolases upon fusion with lysosomes. However, reports of ESCRT-independent surface protein degradation are emerging suggesting that alternative, non-canonical pathways exist. Using Saccharomyces cerevisiae as a model, here we show that in response to substrates, protein misfolding or TOR signaling, some internalized surface transporters (Hxt3, Itr1, Aqr1) bypass ESCRTs en route to the lysosome membrane where they are sorted into an area that is internalized as an intralumenal fragment (ILF) and degraded upon organelle fusion. This ILF pathway also degrades typical ESCRT client proteins (Mup1, Can1, Ste3) when ESCRT function is impaired. As the underlying machinery is conserved, we speculate that the ILF pathway is an important contributor to receptor and transporter down-regulation in all eukaryotes.