Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Orphan receptor GPR37L1 remains unliganded

The Original Article was published on 19 December 2016

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Fig. 1: The corrected GPR37L1 construct does not have the apparent Gαs constitutive activity seen with p426-r37L1.
Fig. 2: The corrected GPR37L1 construct does not display constitutive or ligand-induced activity in any assays examined.

Data availability

Source data are provided with this paper.


  1. 1.

    Ngo, T. et al. Orphan receptor ligand discovery by pickpocketing pharmacological neighbors. Nat. Chem. Biol. 13, 235–242 (2017); retraction (2021).

  2. 2.

    Marazziti, D. et al. Precocious cerebellum development and improved motor functions in mice lacking the astrocyte cilium-, patched 1-associated Gpr37l1 receptor. Proc. Natl Acad. Sci. USA 110, 16486–16491 (2013).

    CAS  Article  Google Scholar 

  3. 3.

    Giddens, M. M. et al. GPR37L1 modulates seizure susceptibility: evidence from mouse studies and analyses of a human GPR37L1 variant. Neurobiol. Dis. 106, 181–190 (2017).

    CAS  Article  Google Scholar 

  4. 4.

    Coleman, J. L. et al. Metalloprotease cleavage of the N terminus of the orphan G protein-coupled receptor GPR37L1 reduces its constitutive activity. Sci. Signal. 9, ra36 (2016); retraction 612, eaba2063 (2019).

  5. 5.

    Jiang, L. I. et al. Use of a cAMP BRET sensor to characterize a novel regulation of cAMP by the sphingosine 1-phosphate/G13 pathway. J. Biol. Chem. 282, 10576–10584 (2007).

    CAS  Article  Google Scholar 

  6. 6.

    Meyer, R. C., Giddens, M. M., Schaefer, S. A. & Hall, R. A. GPR37 and GPR37L1 are receptors for the neuroprotective and glioprotective factors prosaptide and prosaposin. Proc. Natl Acad. Sci. USA 110, 9529–9534 (2013).

    CAS  Article  Google Scholar 

  7. 7.

    Liu, B. et al. Glio- and neuro-protection by prosaposin is mediated by orphan G-protein coupled receptors GPR37L1 and GPR37. Glia 66, 2414–2426 (2018).

    Article  Google Scholar 

  8. 8.

    Inoue, A. et al. TGFα shedding assay: an accurate and versatile method for detecting GPCR activation. Nat. Methods 9, 1021–1029 (2012).

    CAS  Article  Google Scholar 

  9. 9.

    Zheng, X., Asico, L. D., Ma, X. & Konkalmatt, P. R. G protein-coupled receptor 37L1 regulates renal sodium transport and blood pressure. Am. J. Physiol. Ren. Physiol. 316, F506–F516 (2019).

    Article  Google Scholar 

  10. 10.

    Foster, S. R. et al. Discovery of human signaling systems: pairing peptides to G protein-coupled receptors. Cell 179, 895–908 (2019).

    CAS  Article  Google Scholar 

  11. 11.

    Myers, B. R., Neahring, L., Zhang, Y., Roberts, K. J. & Beachy, P. A. Rapid, direct activity assays for Smoothened reveal Hedgehog pathway regulation by membrane cholesterol and extracellular sodium. Proc. Natl Acad. Sci. USA 114, E11141–E11150 (2017).

    CAS  Article  Google Scholar 

  12. 12.

    Morita, N. et al. GPR31-dependent dendrite protrusion of intestinal CX3CR1+ cells by bacterial metabolites. Nature 566, 110–114 (2019).

    CAS  Article  Google Scholar 

  13. 13.

    Rabal, O., Castellar, A. & Oyarzabal, J. Novel pharmacological maps of protein lysine methyltransferases: key for target deorphanization. J. Cheminform. 10, 32 (2018).

    Article  Google Scholar 

  14. 14.

    Castleman, P. N., Sears, C. K., Cole, J. A., Baker, D. L. & Parrill, A. L. GPCR homology model template selection benchmarking: global versus local similarity measures. J. Mol. Graph. Model. 86, 235–246 (2019).

    CAS  Article  Google Scholar 

  15. 15.

    Zhou, Q. et al. Common activation mechanism of class A GPCRs. eLife 8, e50279 (2019).

    Article  Google Scholar 

Download references


We would like to thank R.M. Graham from the Victor Chang Cardiac Research Institute, Australia, for helpful discussions, T. Nettleton from UNSW Sydney for assistance with identifying the cloning error and A. Inoue from Tohoku University for providing the AP–TGF-α constructs and helpful advice. Funding was provided by an NHMRC CJ Martin Early Career Fellowship (1145746 to T.N.), the NIH (R01 AI118985 and R01 GM117424 to I.K.) and a National Heart Foundation Future Leader Fellowship (101153 to N.J.S.).

Author information




N.J.S., J.L.J.C., S.S.S. and B.P.W. discovered the cloning error. N.J.S., I.K., T.N., B.P.W., S.S.S. and J.L.J.C. devised the experimental plan for correcting the scientific record. T.N., B.P.W., S.S.S., P.K. and K.K.C. performed experiments. A.M.F. assisted with experimental design. N.J.S., I.K. and T.N. wrote the manuscript with input from all of the authors.

Corresponding authors

Correspondence to Irina Kufareva or Nicola J. Smith.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Source data

Source Data Fig. 1

Statistical source data.

Source Data Fig. 1

Uncropped western blot.

Source Data Fig. 2

Statistical source data.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Ngo, T., Wilkins, B.P., So, S.S. et al. Orphan receptor GPR37L1 remains unliganded. Nat Chem Biol 17, 383–386 (2021).

Download citation


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing