PICK1 PDZ domain plays an important role in the surface expression and agonist-mediated endocytosis of mGluR1.A, schematic depicting the PDZ domain mutant PICK1(KD-AA). B and C, representative images (B) and quantitation (C) showing that knockdown of endogenous PICK1 decreases the surface expression of myc-mGluR1, and replacement of endogenous PICK1 with PICK1(KD-AA) could not rescue the surface expression of the receptor (N: control = 34; shPICK1 = 34; shPICK1:PICK1(KD-AA) = 34). D and E, representative cells (D) and quantitation (E) of the 100 μM R,S-DHPG–mediated internalization of myc-mGluR1 suggested that acute knockdown of endogenous PICK1 inhibited the endocytosis of the receptor, which could not be rescued by the expression of PICK1(KD-AA) replacement construct (N: control = 34; control + DHPG = 35; shPICK1 + DHPG = 37; shPICK1:PICK1(KD-AA) + DHPG = 31). Results are presented as means ± SD. Scale bar represents 10 μm. ∗∗∗p < 0.001. DHPG, 3, 5-dihydroxyphenylglycine; mGluR, metabotropic glutamate receptor; PICK1, protein interacting with C kinase 1; PDZ, PSD-95/DLG/ZO1.