GPR37L1 Membrane Protein Introduction

Introduction of GPR37L1

GPR37L1, also known as endothelin B receptor-like protein 2 or G-protein coupled receptor 37-like 1, is a protein that encoded by the human GPR37L1 gene. It belongs to the G-protein coupled receptor 1 family. And the complete clone of GPR37L1 had an open reading frame of 1443 base pairs and encoded a 481 amino acid GPCR with 68% similarity and 48% identity to GPR37.

Function of GPR37L1 Membrane Protein

As a member of the Class A rhodopsin-like receptor subfamily of GPCRs, the GPR37L1 was first identified by sequence similarity to the endothelin type B receptor gene, but it is unable to bind endothelin or related peptides. Studies have shown that this orphan receptor is predominantly expressed in the brain and contributes to the cerebellar development and motor skills. In addition, the expression of GPR37L1 is also found in the central nervous system (CNS), heart and gastrointestinal tract. It has been reported that GPR37L1 shares more than 40% amino acid sequence similarity with its close relative GPR37 which is also expressed in the CNS. Moreover, GPR37L1 is involved in the dysregulation of sonic hedgehog (Shh) signaling, which is known to stimulate the proliferation of granule cell precursors and maturation of Bergmann glia. And the deletion of GPR37L1 could lead to precocious cerebellar development and hypertension.

Fig.1 Cell surface receptors for prosaposin. Secreted prosaposin (“PSAP”) can initiate intracellular signaling via binding to GPR37 and GPR37L1. (Meyer, 2014)

Application of GPR37L1 Membrane Protein in Literature

1. Coleman J.L., et.al. Orphan receptor GPR37L1 contributes to the sexual dimorphism of central cardiovascular control. Biology of sex differences. 2018, 9(1):14. PubMed ID: 29625592
   
   

   This article investigates the role of GPR37L1 in blood pressure homeostasis. It suggests that GPR37L1 could regulate baseline blood pressure in female mice and is crucial for cardiovascular compensatory responses in males. Moreover, the expression of GPR37L1 in the brain, yet absence from peripheral cardiovascular tissues, indicates this orphan receptor is a hitherto unknown contributor to central cardiovascular control.

2. Jolly S., et.al. G protein-coupled receptor 37-like 1 modulates astrocyte glutamate transporters and neuronal NMDA receptors and is neuroprotective in ischemia. Glia. 2018, 66(1):47-61. PubMed ID: 28795439
   
   

   This article reveals that GPR37L1 has the ability to protect neurons during ischemia, presumably by modulating extracellular glutamate concentration and NMDAR activation.

3. Giddens M.M., et.al. GPR37L1 modulates seizure susceptibility: Evidence from mouse studies and analyses of a human GPR37L1 variant. Neurobiology of disease. 2017, 106:181-90. PubMed ID: 28688853
   
   

   This article indicates that there is an association between a GPR37L1 variant and a novel progressive myoclonus epilepsy.

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. 2016, 9(423):ra36-. PubMed ID: 27072655
   
   

   This article indicates that GPR37L1 may be a constitutively active receptor, or perhaps its ligand is present under the conditions that we used for analysis, and that the activity of this receptor is instead controlled by signals that regulate metalloprotease activity in the tissue.

5. Marazziti D., et.al. Precocious cerebellum development and improved motor functions in mice lacking the astrocyte cilium-, patched 1-associated Gpr37l1 receptor. Proceedings of the National Academy of Sciences. 2013, 110(41):16486-91. PubMed ID: 24062445
   
   

   This article suggests that the patched 1-associated Gpr37l1 receptor participates in the regulation of postnatal cerebellum development by modulating the Shh pathway.

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Reference

1. Meyer, et.al. (2014). The protective role of prosaposin and its receptors in the nervous system. Brain research, 1585, 1-12.

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