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. 2016 Nov 22;2:16042. doi: 10.1038/celldisc.2016.42

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Copyright © 2016 The Author(s)

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The ECD is a positive regulator and can activate GLP-1R in trans. (a, b) The ECD activates GLP-1R (a) or GLP-1R C347K (b) in trans. Left, cartoon presentation of the TMD (WT/C347K) co-expressed with membrane-tethered ECD (ECD-M) or EX4-ECD fusion (EX4-ECD-M). Dashed orange line indicates the 5xGSA linker between ECD and full-length EX4 peptide. Right, the cAMP signals produced by the TMD in the presence of GLP1R ECD (red bars) versus those induced by the intact GLP-1R or GLP-1R TMD co-expressed with membrane-tethered GCGR ECD (blue bars). All signals are indicated as relative to control (EX4-5xGSA-GLP-1R FL WT, lane 4), which was set as 100%. M: membrane tethered. Error bars=s.d., all experiments were performed as three independent transfection experiments. Two-tailed Student’s t test was used to determine P-values for data points versus control (TMD without co-expressed ECD construct, lane 5, marked by red asterisk). ****⩽0.0001.