“…25 Based on data from phenomics screens, a new model of Nhx1 function emerged proposing that endocytic defects observed in nhx1∆ cells may be caused by MVB membrane fusion defects (Kallay et al, 2011). Lending the greatest support to this hypothesis is the finding that Nhx1 binds Gyp6 (Ali et al, 2004), a Rab-GTPase Activating Protein (Rab-GAP) that 30 inactivates two Rab-GTPases thought to drive membrane fusion (Strom et al, 1993;Vollmer et al, 1999;Will and Gallwitz, 2001): Ypt6, for MVB -Trans-Golgi Network (TGN) vesicle fusion (Bensen et al, 2001;Luo and Gallwitz, 2003;Suda et al, 2013;Brunet et al, 2016) and Ypt7, for MVB -vacuolar lysosome (or vacuole) fusion (Baldehaar et al, 2010;Epp et al, 2011;Baldehaar et al, 2013;Karim et al, 2017). Knocking out GYP6 partially suppresses protein 35 trafficking defects observed in nhx1∆ cells, suggesting that in the absence of NHX1, Gyp6 may inactivate these Rab-GTPases preventing MVB membrane fusion events (Ali et al, 2004).…”