| 2003 |
GPR156 (GABABL) was identified as a novel class C GPCR with homology to GABA(B1) and GABA(B2), containing a putative coiled-coil domain, di-leucine and RXR(R) ER retention motifs in its C-terminus. When expressed alone or with GABA(B1) or GABA(B2), no receptor function in response to GABA(B) ligands was detected, indicating it does not form a functional GABA(B) receptor with known subunits. |
Homology-based cloning, heterologous expression, pharmacological assays |
Brain research. Molecular brain research |
Medium |
12591167
|
| 2003 |
GPR156 (GABABL) protein is broadly distributed in the rat CNS, with dense expression in cortex, hippocampus, dentate gyrus, cerebellum (granule cell layer and Purkinje cells), spinal cord substantia gelatinosa and ventral horn, and a subset of parvalbumin-positive hippocampal interneurons. |
Immunohistochemistry with rabbit polyclonal antisera specific to GABABL protein |
Brain research |
Medium |
14556935
|
| 2021 |
GPR156 exhibits constitutive Gi/o protein coupling activity in the absence of any known ligand, as measured using luciferase reporter assays with G protein chimeras designed to detect intrinsically small constitutive Gi/o signaling. |
Luciferase reporter assays with Gα chimera proteins for Gi/o detection in unliganded receptors |
British journal of pharmacology |
Medium |
33784795
|
| 2021 |
The transcription factor EMX2 polarizes GPR156 distribution at hair cell boundaries; GPR156 then signals through Gαi to trigger a 180° reversal in hair cell orientation. This GPR156-Gαi signaling is essential for establishing mirror-image hair cell orientations in mouse vestibular otolith organs and in zebrafish lateral line neuromasts, and also instructs hair cell reversal in the auditory epithelium. |
Genetic loss-of-function (knockout mice and zebrafish mutants), immunofluorescence localization of GPR156, epistasis analysis with EMX2 and Gαi |
Nature communications |
High |
34001891
|
| 2023 |
STK32A is a downstream effector negatively regulated by EMX2 in hair cells, and STK32A regulates the apical localization of GPR156. In EMX2-positive hair cells, EMX2 represses Stk32a, permitting apical GPR156 enrichment and consequent orientation reversal; ectopic STK32A expression in EMX2-positive regions reorients bundles, and Stk32a loss disrupts GPR156 apical localization. |
Genetic epistasis in double mutant mice (Gpr156 × Stk32a), immunofluorescence, conditional ectopic expression |
eLife |
High |
37144879
|
| 2023 |
GPR156 is identified as a key inducer of lipid droplet accumulation in macrophages lacking MMGT1 during Mycobacterium tuberculosis infection, placing GPR156 in the MMGT1-GPR156-lipid droplet axis that promotes bacterial persistence. |
Genome-wide CRISPR screen, genetic knockdown/knockout validation, lipid droplet quantification in infected macrophages |
Cell host & microbe |
Medium |
37269834
|
| 2024 |
Cryo-EM structures of human GPR156 in Go-free and Go-coupled states reveal that an endogenous phospholipid molecule is located within each transmembrane domain (TMD) of the GPR156 dimer. Asymmetric binding of Gα to the phospholipid-bound GPR156 dimer restructures intracellular loops 1 and 2 and the C-terminal part of TM7 without altering dimer conformation, establishing GPR156 as a transducer for phospholipid signaling and explaining constitutive activity through constant phospholipid binding. |
Cryo-electron microscopy structure determination of apo and G-protein-coupled states, structural analysis of dimer interface and lipid binding site |
Nature structural & molecular biology |
High |
38332368
|
| 2024 |
Cryo-EM structures of human apo GPR156 and the GPR156-Gi3 complex reveal a small extracellular region formed by ECL2 and the N-terminus. GPR156 forms a dimer via a TM5/6–TM5/6 interface in both apo and Gi3-coupled states, indicating high constitutive activity in the apo state. The C-terminus of the G-protein-bound subunit plays a dual role: promoting G protein binding in that subunit while preventing the G-free subunit from binding additional G protein. |
Cryo-EM structure determination of apo GPR156 and GPR156-Gi3 complex, structural analysis of dimer interface and C-terminus function |
Nature communications |
High |
39638804
|
| 2024 |
Loss of GPR156 in zebrafish neuromast hair cells eliminates the smaller mechanically evoked signals characteristic of EMX2-positive hair cells, while mechano-electrical transduction in mouse otolith organ hair cells is normal in Gpr156 mutants, indicating GPR156 relays both orientation and transduction properties downstream of EMX2 in zebrafish but is dispensable for transduction per se in mice. |
Electrophysiology (mechanically evoked signals), loss-of-function in Gpr156 zebrafish and mouse mutants |
eLife |
High |
39531034
|
| 2025 |
GPR156 binds VANGL proteins (core planar cell polarity components) and depends on them for its function in hair cell orientation. However, inhibiting GPR156 signaling facilitates rather than prevents postnatal correction of orientation defects in Vangl and Fzd mutants, indicating GPR156 collaborates with core PCP components to establish orientation but is dispensable—and even inhibitory—for postnatal realignment. |
Genetic epistasis in double mutant mice (Gpr156 × Vangl1/2 and Gpr156 × Fzd3/6 conditional mutants), protein binding/localization assays |
Development (Cambridge, England) |
High |
42063348
|
| 2025 |
Genetic epistasis experiments in mice combining Gpr156 and Stk32a mutations demonstrate: (1) GPR156 functions to reverse stereociliary bundle orientation relative to the PCP axis but can be blocked by STK32A; (2) EMX2 establishes the boundary between the two hair cell groups by repressing Stk32a transcription. These functional relationships hold in both the utricle and cochlea. |
Genetic epistasis in double mutant mice (Gpr156 × Stk32a and Emx2 × Stk32a), hair cell orientation phenotyping |
Journal of cell science |
High |
41208475
|
| 2025 |
A rare missense variant in GPR156 (p.Glu533Asp) found in a Mennonite pedigree with major depressive disorder, when knocked into the murine Gpr156 locus, induces medial habenula hyperactivity and abnormal stress-related behaviors, placing GPR156 in the medial habenula circuitry for mood regulation. |
Humanized knock-in mouse model, in vivo electrophysiology (habenula activity), behavioral assays for stress sensitivity |
Proceedings of the National Academy of Sciences of the United States of America |
Medium |
40228124
|
| 2026 |
Conditional inactivation of Gpr156 specifically in postmitotic hair cells recapitulates the misorientation phenotype of null mutants and results in similar auditory and vestibular dysfunction, demonstrating that GPR156 function is required in hair cells themselves (not surrounding cells) for proper orientation. Mechano-electrical transduction remains intact in the absence of GPR156, establishing that sensory deficits arise from misorientation rather than transduction failure. |
Conditional Cre-mediated knockout in postmitotic hair cells, auditory brainstem response, vestibulo-ocular reflex measurements, hair cell orientation phenotyping |
Scientific reports |
High |
41547998
|