Dietary salt induces taste desensitization via receptor internalization in Drosophila in a sexually dimorphic manner

Sodium homeostasis, which is critical for survival, includes mechanisms for regulating salt intake that integrate central neural pathways with the peripheral taste system. Although the central homeostatic mechanisms of salt appetite are well-studied, the mechanisms by which dietary salt modulates peripheral taste responses remain unclear. We found increased dietary salt reduces salt preference in Drosophila by desensitizing sweet gustatory receptor neurons independent of internal sodium levels. We observed a reversible suppression of salt-evoked neural responses following salt exposure accomplished via clathrin-mediated endocytosis in males and both clathrin- and C-terminal binding protein-dependent endocytosis in females. We also found reversing gustatory receptor neuron sexual identity switched the desensitization pattern, indicating cell-autonomous control of this sexual dimorphism. Moreover, C-terminal binding protein-mediated macropinocytosis in females also dampened sweet taste responses, revealing a sex- and modality-specific mechanism underlying sensory adaptation. These findings reveal dietary experience can affect feeding behavior by reprograming peripheral taste responses, clarifying the plasticity of nutrient sensing.