Rab small GTPases control membrane trafficking through effectors that recruit downstream mediators such as motor proteins. Subcellular trafficking typically involves multiple Rabs, with each specific step mediated by a distinct Rab protein. We describe a collaboration between two distinct Rab-protein-orchestrated trafficking circuits in bladder epithelial cells (BECs) that expels intracellular uropathogenic Escherichia coli (UPEC) from their intracellular niche. RAB11a and RAB27b and their trafficking circuitry are simultaneously involved in UPEC expulsion. While RAB11a recruits its effector RAB11FIP3 and cytoskeletal motor Dynein, RAB27b mobilizes the effector MyRIP and motor Myosin VIIa to mediate bacterial expulsion. This collaboration is coordinated by deposition of the exocyst complex on bacteria-containing vesicles, an event triggered by the innate receptor Toll-like receptor 4. Both RAB11a and RAB27b are recruited and activated by the exocyst complex components SEC6/SEC15. Thus, the cell autonomous defense system can mobilize and coalesce multiple subcellular trafficking circuitries to combat infections.

Rab小GTPases通过效应器控制膜运输，该效应器募集下游介体，例如运动蛋白。亚细胞运输通常涉及多个Rab，每个特定步骤均由不同的Rab蛋白介导。我们描述了膀胱细胞上皮细胞（BECs）中的两个不同的Rab蛋白精心策划的贩运电路之间的合作，驱逐细胞内尿路致病性大肠杆菌（UPEC）来自它们的细胞内利基。RAB11a和RAB27b及其贩运电路同时参与UPEC驱逐。RAB11a募集效应物RAB11FIP3和细胞骨架运动动力蛋白，而RAB27b动员效应物MyRIP和运动肌球蛋白VIIa介导细菌排出。这种协作是通过将囊外复合物沉积在含细菌的囊泡上来协调的，该事件是由先天受体Toll样受体4触发的。RAB11a和RAB27b都被囊外复合物组分SEC6 / SEC15募集并激活。因此，细胞自主防御系统可以动员并合并多个亚细胞贩运回路，以抗击感染。