Glycan sulfation patterns define autophagy flux at axon tip via PTPRσ-cortactin axis.
Nat Chem Biol
; 15(7): 699-709, 2019 07.
Article
em En
| MEDLINE
| ID: mdl-31061498
ABSTRACT
Chondroitin sulfate (CS) and heparan sulfate (HS) are glycosaminoglycans that both bind the receptor-type protein tyrosine phosphatase PTPRσ, 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 PTPRσ 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 PTPRσ. CS activates PTPRσ, which dephosphorylates cortactin-herein identified as a new PTPRσ substrate-and disrupts autophagy flux at the autophagosome-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 PTPRσ and define the fate of axonal regeneration through a mechanism involving PTPRσ, cortactin and autophagy.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Autofagia
/
Sulfatos de Condroitina
/
Cortactina
/
Proteínas Tirosina Fosfatases Classe 5 Semelhantes a Receptores
/
Heparitina Sulfato
/
Regeneração Nervosa
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Nat Chem Biol
Assunto da revista:
BIOLOGIA
/
QUIMICA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Japão