Details

Autor(en) / Beteiligte

• Yamada, Akihiro
• Hikichi, Miyako
• Nozawa, Takashi
• Nakagawa, Ichiro

Titel

FBXO2/SCF ubiquitin ligase complex directs xenophagy through recognizing bacterial surface glycan

Ist Teil von

• EMBO reports, 2021-11, Vol.22 (11), p.e52584-n/a

Ort / Verlag

England: Blackwell Publishing Ltd

Erscheinungsjahr

2021

Link zum Volltext

Quelle

Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals

Beschreibungen/Notizen

• Xenophagy, also known as antibacterial selective autophagy, degrades invading bacterial pathogens such as group A Streptococcus (GAS) to defend cells. Although invading bacteria are known to be marked with ubiquitin and selectively targeted by xenophagy, how ubiquitin ligases recognize invading bacteria is poorly understood. Here, we show that FBXO2, a glycoprotein‐specific receptor for substrate in the SKP1/CUL1/F‐box protein (SCF) ubiquitin ligase complex, mediates recognition of GlcNAc side chains of the GAS surface carbohydrate structure and promotes ubiquitin‐mediated xenophagy against GAS. FBXO2 targets cytosolic GAS through its sugar‐binding motif and GlcNAc expression on the GAS surface. FBXO2 knockout resulted in decreased ubiquitin accumulation on intracellular GAS and xenophagic degradation of bacteria. Furthermore, SCF components such as SKP1, CUL1, and ROC1 are required for ubiquitin‐mediated xenophagy against GAS. Thus, SCFFBXO2 recognizes GlcNAc residues of GAS surface carbohydrates and functions in ubiquitination during xenophagy. Synopsis During xenophagy invading bacteria are marked with ubiquitin, which is then selectively targeted by autophagic membranes. FBXO2 directly recognizes bacterial surface glycan and facilitates SCF complex‐mediated ubiquitination to eliminate bacteria by xenophay. The GlcNAc side chain of the bacterial surface glycan is recognized by FBXO2, a glycoprotein‐specific substrate receptor of the SCF ubiquitin ligase complex. FBXO2 targets invading bacteria via its sugar‐binding motif. FBXO2 and SCF complex components are required for ubiquitin accumulation on intracellular Group A Streptococcus and the cellular defense by xenophagy. FBXO2 directly recognizes bacterial surface glycan and facilitates SCF complex‐mediated ubiquitination to eliminate bacteria by xenophay.