1.F.1.1.5
The RABGET1 (RABEX5) - STX6-VAMP3-VTI1B complex mediates fusion between recycling endosomes and Streptococcus (GAS)-containing autophagosome-like vauoles (Nozawa et al. 2017). Macroautophagy/autophagy plays a critical role in immunity by directly degrading invading pathogens such as Group A Streptococcus (GAS), through a process that has been named xenophagy. Autophagic vacuoles directed against GAS, termed GAS-containing autophagosome-like vacuoles (GcAVs), use recycling endosomes (REs) as a membrane source. This complex mediates fusion between GcAVs and REs. STX6 (syntaxin 6) is recruited to GcAVs and forms a complex with VTI1B and VAMP3 to regulate the GcAV-RE fusion that is required for xenophagy. STX6 targets the GcAV membrane through its tyrosine-based sorting motif and transmembrane domain, and localizes to TFRC (transferrin receptor)-positive punctate structures on GcAVs through its H2 SNARE domain. STX6 is required for the fusion between GcAVs and REs to promote clearance of intracellular GAS by autophagy. VAMP3 and VTI1B interact with STX6 which become localized on the TFRC-positive puncta on GcAVs for RE-GcAV fusion. Knockout of RABGEF1 impairs the RE-GcAV fusion and STX6-VAMP3 interaction. Thus, RABGEF1 mediates RE fusion with GcAVs through the STX6-VAMP3-VTI1B complex.