%0 Journal Article
%T Glycan sulfation patterns define autophagy flux at axon tip via PTPR考-cortactin axis
%J -
%D 2019
%R https://doi.org/10.1038/s41589-019-0274-x
%X Chondroitin sulfate (CS) and heparan sulfate (HS) are glycosaminoglycans that both bind the receptor-type protein tyrosine phosphatase PTPR考, affecting axonal regeneration. CS inhibits axonal growth, while HS promotes it. Here, we have prepared a library of HS octasaccharides and, together with synthetic CS oligomers, we found that PTPR考 preferentially interacts with CS-E〞a rare sulfation pattern in natural CS〞and most HS oligomers bearing sulfate and sulfamate groups. Consequently, short and long stretches of natural CS and HS, respectively, bind to PTPR考. CS activates PTPR考, which dephosphorylates cortactin〞herein identified as a new PTPR考 substrate〞and disrupts autophagy flux at the autophagosome每lysosome fusion step. Such disruption is required and sufficient for dystrophic endball formation and inhibition of axonal regeneration. Therefore, sulfation patterns determine the length of the glycosaminoglycan segment that bind to PTPR考 and define the fate of axonal regeneration through a mechanism involving PTPR考, cortactin and autophagy
%U https://www.nature.com/articles/s41589-019-0274-x