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. 2016 Feb 17;36(7):2131–2147. doi: 10.1523/JNEUROSCI.2921-15.2016

Figure 4.

Figure 4.

Selective disruption of mGlu5-Homer alters agonist-induced signaling to translation initiation and elongation. A, B, Representative Western blots and quantitative group data demonstrate enhanced basal activity of the mTORC1 pathway in acute hippocampal slices from mGlu5R/R compared with WT mice, as measured by P-mTORC1 and P-4EBP (T37/46). Treatment with the Group1 mGluR agonist, DHPG (D; 100 μm; 5 min) increases P-mTORC1 and P-4EBP levels in WT slices, but not mGlu5R/R slices (n = 4–6 mice/genotype). C, D, Enhanced basal activity of translation factors downstream of ERK is observed using Western blots of acute hippocampal slice lysates from mGlu5R/R compared with WT mice, as measured by P-Mnk1, P-eIF4E, and P-4EBP (S65). Although DHPG treatment (100 μm; 5 min) increases P-ERK in mGlu5R/R slices, it fails to increase P-Mnk1, P-eIF4E, and P-4EBP (S65) levels (n = 4–10 mice/genotype). E, F, Enhanced levels of eIF4E coimmunoprecipitation with eIF4G (eIF4E/4G) from lysates of acute hippocampal slices of mGlu5R/R mice, compared with WT mice. Treatment with DHPG increases 4E/4G levels in WT slices, but not in mGlu5R/R slices (n = 6 mice/genotype). G, DHPG treatment of acute hippocampal slices from mGlu5R/R mice results in greater P-EF2, compared with slices from WT mice (n = 15 mice/genotype). H, DHPG treatment results in rapid increases in MAP1b and APP levels in acute hippocampal slices from WT, but not mGlu5R/R mice (n = 9–14 mice/genotype). A–H, Two-way ANOVA; Sidak's post hoc tests. *p < 0.05. **p < 0.01. ***p < 0.001.