<scp>FAM237A</scp>, rather than peptide <scp>PEN</scp> and <scp>proCCK56</scp>‐63, binds to and activates the orphan receptor <scp>GPR83</scp>

Li, Hao-Zheng; Wang, Ya-Fen; Shao, Xin; Liu, Yali; Xu, Zeng‐Guang; Wang, Shilong; Guo, Zhan‐Yun

doi:10.1111/febs.16765

Cited by 10 publications

(13 citation statements)

References 33 publications

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“…While one end of the peptide may be crucial for binding the receptor, an absolute requirement of both peptide termini to be free of another added amino acid (necessary for radioiodination) seems unlikely. Recently, Li and coworkers have confirmed the interaction of FAM237A, but not of PEN, with GPR83 in multiple luminescence-based interaction and activation assays [16]. Their study, like this one, was unable to provide data for binding or activation of PEN with GPR83.…”

Section: Discussionmentioning

confidence: 94%

“…A 2023 paper, however, has comparatively evaluated the capacity of all three ligands proposed so far (PEN, proCCK56-63, and FAM237A) to bind and activate GPR83. Using multiple assay systems, only FAM237A was confirmed as a GPR83 ligand and agonist, but not PEN or proCCK56-63 [16]. The present study was initiated to evaluate PEN as a ligand of GPR83.…”

Section: Introductionmentioning

confidence: 95%

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Is the Neuropeptide PEN a Ligand of GPR83?

Giesecke,

Asimi,

Stulberg

et al. 2023

IJMS

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G protein-coupled receptor 83 (GPR83) is a class A G protein-coupled receptor with predominant expression in the cerebellum and proposed function in the regulation of food intake and in anxiety-like behavior. The neuropeptide PEN has been suggested as a specific GPR83 ligand. However, conflicting reports exist about whether PEN is indeed able to bind and activate GPR83. This study was initiated to evaluate PEN as a potential ligand of GPR83. Employing several second messenger and other GPCR activation assays as well as a radioligand binding assay, and using multiple GPR83 plasmids and PEN peptides from different sources, no experimental evidence was found to support a role of PEN as a GPR83 ligand.

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Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 95%

Is the Neuropeptide PEN a Ligand of GPR83?

Giesecke,

Asimi,

Stulberg

et al. 2023

IJMS

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show abstract

“…Preparation of the mature FAM237B and the N-terminally SmBiT-fused FAM237B (SmBiT-FAM237B) was according to our previous procedure developed for preparation of mature FAM237A (Li et al 2023). Brie y, the intein-fused precursor was solubilized from inclusion bodies via an S-sulfonation approach after overexpression in the Escherichia coli strain BL21(DE3), puri ed by immobilized metal ion a nity chromatography (Ni 2+ column), and then treated by tris(2-carboxyethyl)phosphine and sodium 2mercaptoethanesulfonate under denatured condition to remove the reversibly modi ed sulfonate moieties.…”

Section: Preparation Of Mature Fam237b and The Smbit-fused Version Vi...mentioning

confidence: 99%

“…The NanoBiT-based binding assay was conducted according to our previous procedure (Li et al 2023). Brie y, human embryonic kidney (HEK) 293T cells were transiently transfected with the expression construct pcDNA6/sLgBiT-GPR83 that encodes an N-terminally secretory large NanoLuc fragment (sLgBiT)-fused human GPR83.…”

Section: The Nanobit-based Ligand−receptor Binding Assaymentioning

confidence: 99%

“…The NanoBiT-based β-arrestin recruitment assay was conducted according to our previous procedure (Li et al 2023). Brie y, HEK293T cells were transiently transfected with the expression control vector pCMV-TRE3G (Clontech, Mountain View, CA, USA) and the coexpression construct pTRE3G-BI/GPR83-LgBiT:SmBiT-ARRB2 that encodes a C-terminally LgBiT-fused human GPR83 (LgBiT-GPR83) and an N-terminally SmBiT-fused human β-arrestin 2 (SmBiT-ARRB2) via an inducible bi-directional promoter.…”

Section: Nanobit-based β-Arrestin Recruitment Assaymentioning

confidence: 99%

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Nanomolar range of FAM237B can activate receptor GPR83

Wang

et al. 2023

Preprint

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The orphan G protein-coupled receptor 83 (GPR83) is implicated in the regulation of energy metabolism and certain anxiety-related behaviors. Our recent study confirmed that family with sequence similarity 237 member A (FAM237A), also known as neurosecretory protein GL (NPGL), is an efficient agonist for GPR83, but did not support the proprotein convertase subtilisin/kexin type 1 inhibitor (PCSK1N, also known as proSAAS)-derived peptide PEN and the procholecystokinin-derived peptide proCCK56-63 as ligands of this receptor. FAM237B (also known as NPGM), a paralog of FAM237A, was previously reported as a weak agonist for GPR83 with approximately 100-fold lower activity in an inositol 1-phosphate accumulation assay. In the present study, we prepared mature human FAM237B via an intein-fusion approach and measured its activity towards human GPR83 via a NanoLuc Binary Technology (NanoBiT)-based ligand‒receptor binding assay and a NanoBiT-based b-arrestin recruitment assay. Mature FAM237B displayed moderately lower activity than its paralog FAM237A in these binding and activation assays, but could cause a significant activation effect at the nanomolar range (1‒10 nM). Thus, FAM237B appears to be another endogenous agonist for receptor GPR83.

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Nanomolar range of FAM237B can activate receptor GPR83

Li,

Wang,

et al. 2023

Amino Acids

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The orphan G protein-coupled receptor 83 (GPR83) is implicated in the regulation of energy metabolism and certain anxiety-related behaviors. Our recent study confirmed that family with sequence similarity 237 member A (FAM237A), also known as neurosecretory protein GL (NPGL), is an efficient agonist for GPR83, but did not support the proprotein convertase subtilisin/kexin type 1 inhibitor (PCSK1N, also known as proSAAS)-derived peptide PEN and the procholecystokinin-derived peptide proCCK56-63 as ligands of this receptor. FAM237B (also known as NPGM) is a paralog of FAM237A that was previously reported as a weak agonist for GPR83 with approximately 100-fold lower activity in an inositol 1-phosphate accumulation assay.In the present study, we prepared mature human FAM237B via an intein-fusion approach and measured its activity towards human GPR83 via a NanoLuc Binary Technology (NanoBiT)-based ligand receptor binding assay and a NanoBiT-based β-arrestin recruitment assay. Mature FAM237B displayed moderately lower activity than its paralog FAM237A in these binding and activation assays, but could cause a significant activation effect at the nanomolar range (1 10 nM). Thus, FAM237B appears to be another endogenous agonist for receptor GPR83.

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FAM237A, rather than peptide PEN and proCCK56‐63, binds to and activates the orphan receptor GPR83

Abstract: Hao-Zheng Li and Ya-Fen Wang contributed equally to this work.

Cited by 10 publications

References 33 publications

Is the Neuropeptide PEN a Ligand of GPR83?

Is the Neuropeptide PEN a Ligand of GPR83?

Nanomolar range of FAM237B can activate receptor GPR83

Nanomolar range of FAM237B can activate receptor GPR83

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