GBP-mediated restriction of Toxoplasma in murine cells.
In murine cells, type II and III Toxoplasma vacuoles are attacked by a range of host proteins leading to the disruption of the vacuolar membrane. The ‘GMS’ IRGs (not shown) block ‘GKS’ IRG activation. Once activated, ‘GKS’ IRGs accumulate on the vacuole and recruit an unknown seeding E3 ubiquitin ligase, as well as the p62-interacting E3 ubiquitin ligases TRAF6 and TRIM21. GBPs target to the vacuole via p62-dependent and independent mechanisms. Ubiquitination of the vacuole is of the K48 and K63 linkage type on substrate proteins that potentially include IRGs and GBPs themselves. Rupture of the vacuole is dependent on IRGs, GBPs and p62.