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. 2023 Dec 6;9(49):eadi8076. doi: 10.1126/sciadv.adi8076

Fig. 7. Heterodimerization reshapes the trafficking fates of mGluRs.

Fig. 7.

(A and B) Confocal images of fixed HEK 293T cells expressing SNAP-mGluR8 with Halo-mGluR2 (A) or Halo-mGluR3 (B) and treated with glutamate (30 min) showing colocalization with Lamp1-YFP. SNAP and Halo tags are labeled with BG–Alexa-546 and CA-Sulfo646, respectively. Merged images are from area in dotted boxes. Scale bar, 5 μm. (C) Summary of PCC analysis showing colocalization of coexpressed mGluR constructs with Lamp1-YFP. Substantial colocalization is seen for all subtypes only in conditions including mGluR8 expression. (D) Total fluorescence measurement of SNAP-mGluR2 when coexpressed with unlabeled mGluR2, mGluR3, or mGluR8. Only mGluR8 coexpression enables a glutamate-driven reduction in total mGluR2 fluorescence intensity (i.e., degradation). (E) Total fluorescence measurement of SNAP-mGluR3 when coexpressed with unlabeled mGluR3 or mGluR8. Only mGluR8 coexpression enables a glutamate-driven reduction in total mGluR3 fluorescence intensity. (F) Total fluorescence measurement of SNAP-mGluR8 when coexpressed with unlabeled Halo-mGluR8, mGluR3, or mGluR2. All coexpression conditions show a glutamate-driven reduction in total fluorescence intensity. (G) Schematic summarizing the main findings regarding the β-arrs coupling, internalization, and trafficking of mGluR2-, mGluR3-, and mGluR8-containing homo- and heterodimers. One-way ANOVA test, *P < 0.05, **P < 0.01, and ***P < 0.001. Data are represented as means ± SEM.