Figure 4.

Altered SNX27/GPR17 interaction and impaired myelination in a mouse model of DS. During physiological oligodendrocyte maturation, GPR17 must be downregulated at a specific step of oligodendrocyte differentiation to allow the transition from mature to fully myelinating cells. SNX27 promotes and controls oligodendrocyte maturation, by guiding the membrane recycling and degradation of GPR17 receptor through the binding to a type I PDZ-binding motif located at its C-terminus. In the brains of Ts65Dn mice (an animal model of DS), trisomic miR-155 leads to SNX27 degradation, which in turn dysregulates GPR17 membrane expression leading to its precocious downregulation. We hypothesize that this event is crucially related to the altered pattern of myelination observed in Ts65Dn mouse brains, with reduced expression of myelin proteins, which could significantly affect cognitive functions. See text and Meraviglia et al. (2016) for details.