Lipid binding of PICK1 is required for regulating ASIC1a-mediated acidotoxicity. A, ASIC1a with wild-type PICK1, lipid binding-deficient mutant PICK1 2K-E or PDZ mutant PICK1 KD-AA were transfected into COS7 cells. Cell toxicity study was then performed as in Fig. 5. B, The percentage of cell death was quantified from multiple experiments. Wild-type PICK1 co-transfection showed significantly more cell death in response to acidosis compared with mutant PICK1 co-transfection (** p < 0.01, *** p < 0.001). There was no further increase of cell death in PICK1 2K-E and PICK1 KD-AA co-transfected cells compared with ASIC1a-only transfected cells (p > 0.05).