Title :

Glycan sulfation patterns define autophagy flux at axon tip via PTPRσ-cortactin axis

Author(s) :

Sakamoto, Kazuma [Auteur]
Ozaki, Tomoya [Auteur]
Ko, Yen-Chun [Auteur]
Tsai, Cheng-Fang [Auteur]
Gong, Yuanhao [Auteur]
Morozumi, Masayoshi [Auteur]
Ishikawa, Yoshimoto [Auteur]
Uchimura, Kenji [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Nagoya University
Nadanaka, Satomi [Auteur]
Kitagawa, Hiroshi [Auteur]
Zulueta, Medel Manuel L. [Auteur]
Bandaru, Anandaraju [Auteur]
Tamura, Jun-ichi [Auteur]
Hung, Shang-Cheng [Auteur]
Kadomatsu, Kenji [Auteur]

Journal title :

Nature Chemical Biology

Abbreviated title :

Nat Chem Biol

Volume number :

15

Pages :

699-709

Publisher :

Springer Nature

Publication date :

2019-05-06

English keyword(s) :

Carbohydrates
Chemical libraries
Glycobiology
Neurological disorders

HAL domain(s) :

Sciences du Vivant [q-bio]
Chimie/Chimie théorique et/ou physique

English abstract : [en]

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. ...
Show more >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.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Université de Lille
CNRS

Collections :

• Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576

Research team(s) :

Diversité structurale des héparanes sulfates et régulation de la réponse inflammatoire

Submission date :

2020-12-14T10:40:27Z
2020-12-17T10:27:48Z