Selective rescue of the acidification-independent function accelerates degeneration by increasing accumulations in Syx7-positive, degradation-incompetent compartments. (A) Summary of V100 functions and v100^R755A rescue data. Our findings indicate two acidification-independent functions that are rescued by v100^R755A: synaptic vesicle (SV) fusion through Syx1A interaction and early endosomal (EE) fusion through Syx7 interaction. In contrast, V100 has a function as part of the V0V1 holoenzyme once endosomes mature into degradative compartments that are not rescued by v100^R755A. Consequently, selective rescue of the acidification-independent function leads to increased accumulations in Syx7-positive, degradation-incompetent compartments. (B, C, and D) 1-d adult photoreceptor terminals for control (B), v100-null mutant (C), and v100^R755A rescue in the v100 mutant (D). (B’, C’, and D’) Chaoptin alone (green channel) is shown. (B’’, C’’, and D’’) Syx7 alone (magenta channel) is shown. In the v100^R755A rescue, most chaoptin accumulates in large, Syx7-encircled MVB-like structures (arrows). RE, recycling endosome; RV, recycling vesicle. Bar, 5 µm.