Affinage

GPR143

G-protein coupled receptor 143 · UniProt P51810

Length
404 aa
Mass
43.9 kDa
Annotated
2026-06-10
100 papers in source corpus 27 papers cited in narrative 27 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GPR143 (OA1) is an intracellular seven-transmembrane G-protein-coupled receptor that governs melanosome biogenesis and serves more broadly as an L-DOPA sensor coupling endolysosomal organelle dynamics to G-protein signaling (PMID:18828673, PMID:17920058, PMID:16303920). It is targeted to lysosomes and melanosomes by two independent, unconventional sorting signals—a dileucine motif in the third cytosolic loop and a WE doublet in the C-tail—both of which must be disrupted to redirect the receptor to the plasma membrane (PMID:16621890), and it adopts a 7TM topology with its C-terminus facing the cytoplasm (PMID:17920058). L-DOPA is its endogenous agonist, triggering calcium influx and beta-arrestin recruitment, with dopamine acting as a competing antagonist (PMID:18828673); arrestins in turn downregulate signaling (PMID:16524428). Activated GPR143 couples selectively to Gαi3—not Gαi1 or Gαi2—and Gαi3 is the genetic downstream effector, since constitutively active Gαi3 rescues the melanosome phenotype of Oa1-null RPE (PMID:18378571, PMID:21931697, PMID:24098784). Through this pathway it controls melanosome number at early maturation stages and melanosome size at stage IV, with loss of function producing giant macromelanosomes and optic pathway misrouting (PMID:11092754, PMID:16303920), and it acts via an MITF→PMEL transcriptional cascade and partners including the escort protein MART-1 and melanoregulin, which links it to the BLOC-2 pathway (PMID:19717472, PMID:24650003, PMID:22984402). Mechanistically, GPR143 is ubiquitinated and sorted through the ESCRT machinery into intraluminal vesicles, selectively delaying PMEL-MVB delivery to lysosomes to commit cargo to melanosome biogenesis (PMID:21730137, PMID:24006264), and it more generally drives ESCRT-dependent exosome biogenesis by recruiting the ESCRT-0 subunit HRS to cargo such as EGFR, promoting cancer cell motility through integrin/FAK/Src signaling (PMID:36800996). In the nervous system and vasculature it functions as an L-DOPA receptor that forms TM-domain-specific heteromers: a TM5 interaction potentiates dopamine D2 receptor signaling (potentiating D2L while suppressing D2S) and a TM2 interaction with adrenergic α1B receptor augments their signaling (PMID:24117106, PMID:36807226, PMID:37394637, PMID:39179337). It promotes hippocampal neurogenesis and regulates mood in a dopamine-independent manner (PMID:35257172), and inhibits neurite outgrowth via Gα13 and L-type calcium channels (PMID:31606330, PMID:39068034). Missense mutations cause ocular albinism either by ER retention/misfolding or by disrupting cytosolic-loop residues required for G-protein coupling (PMID:11115845).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2000 High

    Establishing the physiological consequence of GPR143 loss showed that the receptor is required for melanosome size control and normal optic pathway wiring, defining the cellular basis of ocular albinism.

    Evidence Gene-targeted Oa1 knockout mouse with RPE electron microscopy and retinofugal pathway tracing

    PMID:11092754

    Open questions at the time
    • Did not define the molecular signaling mechanism producing macromelanosomes
    • Mechanism of optic fiber misrouting not established
  2. 2000 High

    Systematic mutant analysis resolved how disease alleles fail, separating folding/trafficking defects from signaling defects and implicating the cytosolic loops in effector coupling.

    Evidence Expression of 19 missense mutants in COS-7 cells with localization and glycosylation readouts

    PMID:11115845

    Open questions at the time
    • G-protein identity not yet known
    • No structural model of the coupling interface
  3. 2006 High

    Defining the receptor's intracellular addressing and constitutive signaling competence showed GPR143 is a bona fide GPCR delivered to lysosomes/melanosomes by two unconventional sorting signals and regulated by arrestins.

    Evidence Chimeric LAMP1 fusion constructs and mutagenesis for sorting; COS7 G-protein activation, phosphorylation, and arrestin co-IP

    PMID:16524428 PMID:16621890

    Open questions at the time
    • Endogenous ligand not identified
    • Specific Gα subunit not defined
  4. 2007 High

    Direct topology mapping confirmed GPR143 spans the endolysosomal membrane seven times with a cytoplasmic C-terminus, validating its classification as an intracellular 7TM GPCR.

    Evidence HA-tag accessibility with selective permeabilization in COS-1 cells

    PMID:17920058

    Open questions at the time
    • Does not address ligand access from the organelle lumen
    • No high-resolution structure
  5. 2008 High

    Identifying L-DOPA as the endogenous agonist and dopamine as antagonist established the receptor's pharmacology and linked activation to calcium, beta-arrestin, and an RPE PEDF autocrine loop.

    Evidence Radioligand binding, calcium and beta-arrestin assays, and PEDF secretion in RPE and transfected cells

    PMID:18828673

    Open questions at the time
    • How a soluble metabolite reaches the intracellular receptor not defined
    • Did not link ligand binding to melanosome phenotypes in vivo
  6. 2008 High

    Coupling the receptor to a specific G protein, Gαi co-IP and Gαi3-knockout phenocopy placed Gαi3 in the OA1 melanosome pathway.

    Evidence Co-IP from melanocytes plus genetic epistasis comparing Gαi3-/- and Oa1-/- mice

    PMID:18378571

    Open questions at the time
    • Did not distinguish among Gαi isoforms
    • Direct effector mechanism not yet shown
  7. 2011 High

    Refining and proving the effector relationship demonstrated Gαi3-selective binding and a reciprocal stability dependence, and ubiquitination/ESCRT studies revealed how the receptor is sorted into intraluminal vesicles.

    Evidence GST pull-down and co-IP across Gαi knockouts; ubiquitination assays with ESCRT depletion and EM

    PMID:21730137 PMID:21931697

    Open questions at the time
    • The ubiquitin ligase acting on GPR143 not identified
    • Link between Gαi3 signaling and ESCRT sorting not integrated
  8. 2013 High

    Genetic rescue with constitutively active Gαi3 in Oa1-null RPE proved Gαi3 is the downstream effector, and parallel work showed OA1 activity selectively delays PMEL-MVB lysosomal delivery.

    Evidence Lentiviral Gαi3(Q204L) transgenesis with EM morphometry; OA1 wild-type/mutant expression in PMEL-HeLa cells with MVB and cargo assays

    PMID:24006264 PMID:24098784

    Open questions at the time
    • How Gαi3 activity translates into MVB sorting decisions not resolved
    • Cargo selectivity mechanism not defined
  9. 2009 Medium

    Identifying protein partners that stabilize and route the receptor and organelle (MART-1, melanoregulin/BLOC-2) and the OA1→MITF→PMEL cascade connected GPR143 to the broader melanosome biogenesis machinery.

    Evidence Co-IP and siRNA with EM in melanocytes (MART-1); co-IP and genetic rescue (MREG); loss-of-function/rescue with MITF/PMEL readouts

    PMID:19717472 PMID:22984402 PMID:24650003

    Open questions at the time
    • Whether MITF regulation is direct or downstream of signaling unresolved
    • Stoichiometry and order of partner assembly not defined
  10. 2014 High

    Demonstrating GPR143 acts as a functional L-DOPA receptor in defined CNS and vascular contexts extended its role beyond pigmentation to neurogenesis, mood, cardiovascular regulation, and neurite outgrowth.

    Evidence In vivo shRNA and antagonism in the NTS; Gpr143 knockout mice/rats with neurogenesis, behavioral, and pulmonary artery assays; PC12 neurite assays with Gα13 knockdown and L-type Ca2+ blockers

    PMID:24117106 PMID:31606330 PMID:35063136 PMID:35257172 PMID:39068034

    Open questions at the time
    • G-protein/effector coupling differs across tissues and is incompletely mapped
    • Dopamine-independence mechanism in neurogenesis not fully resolved
    • A negative result shows L-DOPA-induced ptosis is GPR143-independent (PMID 27622543), bounding its pharmacology
  11. 2023 High

    Revealing TM-domain-specific heteroreceptor complexes showed GPR143 directly modulates other GPCRs—potentiating DRD2 via TM5 and ADRA1B via TM2—and that it drives ESCRT-dependent exosome biogenesis with cancer-relevant cargo via HRS.

    Evidence Chimeric domain-swap, co-IP, cAMP/ERK/GSK3β assays, in vivo peptide disruption and conditional knockouts (DRD2/ADRA1B); co-IP, exosome proteomics, and in vivo cancer models (HRS/EGFR)

    PMID:36800996 PMID:36807226 PMID:37394637 PMID:38286627 PMID:39179337

    Open questions at the time
    • Structural basis of TM-interface heteromerization not solved
    • How a melanosomal receptor reaches the plasma membrane to engage cell-surface GPCRs not reconciled
    • Generality of HRS-cargo sorting beyond EGFR/integrins not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single intracellular L-DOPA receptor integrates G-protein coupling, ESCRT-dependent sorting, and surface heteroreceptor complexes into tissue-specific outputs remains unresolved.
  • No structure of GPR143 alone or in complex
  • Mechanism reconciling melanosomal/endolysosomal localization with plasma-membrane heteromer function unknown
  • Unified model linking Gαi3, Gα13, and arrestin branches across tissues lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 3 GO:0098772 molecular function regulator activity 3 GO:0060090 molecular adaptor activity 2
Localization
GO:0005764 lysosome 3 GO:0005886 plasma membrane 3 GO:0005768 endosome 2 GO:0043226 organelle 2
Pathway
R-HSA-112316 Neuronal System 3 R-HSA-162582 Signal Transduction 3 R-HSA-1852241 Organelle biogenesis and maintenance 3 R-HSA-5653656 Vesicle-mediated transport 3
Partners
ADRA1BDRD2EGFRGNA13GNAI3HGSMLANAMREG
Complex memberships
BLOC-2 (via melanoregulin)ESCRT-0 (via HRS)

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2008 L-DOPA is an endogenous ligand for OA1/GPR143. Radiolabeled ligand binding confirmed a single, saturable binding site for L-DOPA. OA1 activation by L-DOPA triggers intracellular calcium influx and beta-arrestin recruitment. Dopamine competed with L-DOPA for the OA1 binding site, suggesting it acts as an antagonist. OA1 stimulation in RPE with L-DOPA results in increased PEDF secretion, forming an autocrine loop with tyrosinase. Radiolabeled ligand binding assay, intracellular calcium influx measurement, beta-arrestin recruitment assay, PEDF secretion assay, tyrosinase inhibition experiments in RPE cells and transfected cell lines PLoS biology High 18828673
2006 OA1 expressed in COS7 cells activates heterotrimeric G proteins spontaneously. OA1 mutants with missense mutation or deletion in the third cytosolic loop lack this ability. OA1 is phosphorylated, colocalizes and coprecipitates with arrestins, and arrestins downregulate OA1 signaling by reducing its expression levels. Heterologous expression in COS7 cells, G protein activation assay, co-immunoprecipitation with arrestins, colocalization immunofluorescence, phosphorylation assay Pigment cell research High 16524428
2006 OA1 intracellular targeting to lysosomes and melanosomes requires two separate sorting signals: an unconventional dileucine motif in the third cytosolic loop and a novel tryptophan-glutamic acid (WE) doublet in the C-terminal tail. Both motifs must be simultaneously mutated to redirect OA1 to the plasma membrane, indicating they independently drive intracellular targeting. Chimeric protein constructs (OA1 cytosolic domains fused to LAMP1 lumenal/TM domains), missense and deletion mutagenesis, subcellular localization by immunofluorescence in melanocytic and non-melanocytic cells Journal of cell science High 16621890
2007 OA1, properly localized to intracellular lysosomal organelles, spans the membrane seven times with its C-terminus directed to the cytoplasm, confirming its topology as an intracellular 7-transmembrane GPCR. HA-tag insertion into predicted cytosolic/luminal regions, selective plasma membrane permeabilization leaving endolysosomal membranes intact, immunofluorescence accessibility assay in COS-1 cells Experimental eye research High 17920058
2009 OA1 interacts biochemically with the premelanosomal protein MART-1. MART-1 loss by siRNA reduces OA1 stability and causes similar defects in premelanosome biogenesis and composition, indicating MART-1 acts as an escort protein for OA1. OA1 loss of function leads to decreased pigmentation and formation of enlarged aberrant premelanosomes with disorganized fibrillar structures displaying mislocalized mature melanosome and lysosome membrane proteins. siRNA inactivation of OA1 and MART-1 in human pigmented melanocytic cells, co-immunoprecipitation, electron microscopy of melanosome ultrastructure, immunofluorescence of melanosomal protein localization Human molecular genetics High 19717472
2008 OA1 coimmunoprecipitates with the Gαi subunit of heterotrimeric G proteins from human melanocyte extracts. Gαi3-deficient mice phenocopy Oa1-deficient mice with reduced melanosome density, enlarged melanosomes, and reduced ipsilateral retinofugal projections, placing Gαi3 in the same pathway as OA1. Co-immunoprecipitation from human melanocyte extracts; genetic epistasis using Gαi3-/- and Oa1-/- mouse models; light and electron microscopy of RPE melanosomes; retrograde labeling of optic pathway Investigative ophthalmology & visual science High 18378571
2011 Among Gαi subfamily members, Gαi3 specifically binds to Oa1. GST pull-down and immunoprecipitation assays demonstrate that only Gαi3 (not Gαi1 or Gαi2) interacts with Oa1. Gαi3 expression is barely detectable in Oa1-/- RPE, indicating Oa1 is required for Gαi3 stability in this tissue. GST pull-down, co-immunoprecipitation, Western blotting in Gαi1-/-, Gαi2-/-, Gαi3-/- and double knockout mice, RPE morphometry by electron microscopy PloS one High 21931697
2013 A constitutively active Gαi3 (Q204L) expressed in the RPE of Oa1-/- mice rescues the normal melanosomal phenotype, restoring higher melanosome density and normal small melanosome size, demonstrating that Gαi3 is the downstream effector of Oa1 in melanosome biogenesis. Lentiviral transgenesis of constitutively active Gαi3(Q204L) in Oa1-/- RPE; electron microscopy morphometry; PCR, Southern, Western blot, confocal microscopy for transgene confirmation PloS one High 24098784
2011 OA1 is ubiquitinated, and its intracellular sorting and degradation require functional ESCRT-0, -I, and -III components. OA1 ubiquitination is specifically required for its targeting to intraluminal vesicles of multivesicular endosomes, regulating the balance between degradation and delivery to melanosomes. Biochemical ubiquitination assays, overexpression and siRNA depletion of ESCRT subunits, morphological analysis by immunofluorescence and electron microscopy Proceedings of the National Academy of Sciences of the United States of America High 21730137
2023 GPR143 controls ESCRT-dependent exosome biogenesis by interacting with HRS (ESCRT-0 subunit) and promoting HRS association with cargo proteins such as EGFR, enabling selective protein sorting into intraluminal vesicles in multivesicular bodies. GPR143-driven exosome secretion carries integrin signaling proteins and promotes cancer cell motility/invasion through the integrin/FAK/Src pathway. Co-immunoprecipitation of GPR143 with HRS and EGFR; quantitative proteomics and RNA profiling of exosomes; gain- and loss-of-function in mouse cancer models; cell motility/invasion assays Developmental cell High 36800996
2013 OA1 expression (but not signaling-deficient OA1 mutants) increases MVB numbers and inhibits lysosomal delivery of PMEL-containing MVBs without affecting EGFR-containing MVB degradation, indicating OA1 activity selectively delays PMEL-MVB fusion with lysosomes to allow commitment to melanosome biogenesis. OA1 wild-type and inactivating mutant expression in HeLa cells expressing PMEL; quantification of MVB numbers by electron microscopy; EGFR degradation assay; PMEL delivery to lysosome assay Journal of cell science High 24006264
2000 Missense mutations in OA1 cause two distinct biochemical defects: ~60% cause ER retention with defective glycosylation (protein misfolding), while ~40% traffic normally but cluster in the second and third cytosolic loops critical for G protein coupling and effector activation. Expression of 19 missense mutants in COS-7 cells, analysis of subcellular distribution by immunofluorescence, glycosylation analysis by biochemical methods Human molecular genetics High 11115845
2000 Oa1 knockout mice display giant melanosomes (macromelanosomes) in RPE formed by abnormal growth of single melanosomes rather than fusion, and show reduced size of the uncrossed retinofugal pathway (optic fiber misrouting), establishing Oa1 as required for melanosome size regulation and normal optic pathway development. Gene targeting knockout mouse; electron microscopy of RPE; retrograde labeling of retinofugal pathway; ophthalmologic examination Human molecular genetics High 11092754
2005 Oa1 controls melanosome biogenesis at two stages: at early maturation stages it controls the abundance (number) of melanosomes in RPE cells, and at later stages (stage IV) it controls organelle size. This was established using double-knockout mice combining Oa1 null with either Tyr or Matp mutations that block melanosome maturation at stages II and III respectively. Genetic epistasis with double-knockout mice (Oa1-/-;Tyr(c-2J) and Oa1-/-;Matp(uw)); electron microscopy morphometry; immunohistochemistry of tyrosinase activity Investigative ophthalmology & visual science High 16303920
2014 OA1 loss of function reduces basal and α-MSH/cAMP-induced MITF expression, which in turn reduces PMEL expression without affecting tyrosinase or melanin levels. OA1 re-expression rescues melanosome biogenesis and activates MITF expression, establishing an OA1→MITF→PMEL transcriptional cascade for melanosome quality control. OA1 loss-of-function and rescue in melanocytes; qRT-PCR and Western blot for MITF and PMEL; α-MSH stimulation assays; melanosome morphometry Pigment cell & melanoma research Medium 24650003
2012 Melanoregulin (MREG) interacts with both BLOC-2 complex members and Oa1, linking the BLOC pathway to Oa1 in melanosome size regulation. Transgenic overexpression of melanoregulin in Oa1-knockout mice corrects macromelanosome size in RPE, while MREG loss enlarges micromelanosomes in BLOC-2 mutants. Co-immunoprecipitation of MREG with Oa1 and BLOC-2 members; Oa1 knockout mouse crossed with MREG transgenic mouse; electron microscopy of RPE melanosomes PloS one Medium 22984402
2014 OA1/GPR143 functions as a receptor for L-DOPA in the nucleus tractus solitarii (NTS) in vivo. OA1 shRNA knockdown in the NTS blocked depressor and bradycardic responses to microinjected L-DOPA but not to glutamate. A competitive OA1 antagonist (DOPA cyclohexyl ester) suppressed phenylephrine-induced bradycardic responses. Immunohistochemistry of OA1 in NTS; adenoviral shRNA knockdown of OA1 in NTS; blood pressure and heart rate measurements after DOPA microinjection in anesthetized rats; pharmacological antagonism British journal of pharmacology High 24117106
2015 Morpholino-mediated knockdown of OA1 in zebrafish RPE induces a major reduction in melanosome number, recapitulating the mammalian disease. Melanosome number (controlled by OA1) and melanosome shape (controlled by PMEL) are independently regulated, and cylindrical but not spherical melanosomes enter apical processes. Morpholino knockdown of OA1 in zebrafish; electron microscopy; analysis of melanosome movement into apical processes Journal of cell science Medium 25690007
2023 GPR143 potentiates dopamine D2 receptor (DRD2) signaling through a direct physical interaction at the fifth transmembrane domain of GPR143. L-DOPA enhances the GPR143–DRD2 interaction and augments quinpirole-induced decrease in cAMP levels in cells co-expressing both receptors. A peptide disrupting the GPR143–DRD2 interaction mitigated DRD2-mediated behavioral effects in vivo. GPR143 selectively potentiates DRD2/D2L but not DRD1 or DRD3. Co-immunoprecipitation in cells co-expressing GPR143 and DRD2/DRD1/DRD3; cAMP assay; chimeric domain-swap analysis (GPR143 TM domains replaced with GPR37); intracerebroventricular peptide injection disrupting interaction; behavioral analysis in Gpr143-/y mice Journal of neurochemistry High 36807226
2024 GPR143 expressed in striatal cholinergic interneurons enhances DRD2-mediated haloperidol-induced catalepsy. Co-expression of GPR143 increases cell surface expression of DRD2, and L-DOPA application further enhances DRD2 surface expression. GPR143 regulates cholinergic interneuron firing pause duration. Cholinergic interneuron-specific Gpr143 conditional knockout (Chat-cre;Gpr143flox/y); striatal slice electrophysiology; surface DRD2 expression assay in CHO cells; ribosomal protein S6 phosphorylation in dorsolateral striatum; behavioral catalepsy assay The Journal of neuroscience High 38286627
2023 GPR143 interacts with adrenergic α1B receptor (ADRA1B) at the second transmembrane (TM2) domain interface. A TAT-TM2 peptide disrupts the GPR143–ADRA1B interaction and suppresses GPR143-mediated augmentation of phenylephrine-induced ERK phosphorylation. Chimeric domain-swap analysis (TM domains of GPR143 replaced with GPR37); co-immunoprecipitation of GPR143 and ADRA1B; ERK phosphorylation assay; TAT-fused TM2 peptide disruption in HEK293T cells Biological & pharmaceutical bulletin Medium 37394637
2019 Overexpression of wild-type GPR143 (but not its disease-associated mutants) inhibits neurite outgrowth in NGF-treated PC12 cells. This inhibition is mitigated by the OA1 antagonist DOPA cyclohexyl ester and by knockdown of Gα13, placing Gα13 downstream of GPR143 in the neurite inhibition pathway. Overexpression of wild-type and mutant GPR143 in PC12 cells; neurite outgrowth measurement; pharmacological antagonism; Gα13 siRNA knockdown Journal of pharmacological sciences Medium 31606330
2024 GPR143-induced inhibition of neurite outgrowth in PC12 cells is mediated via L-type calcium channels. Nifedipine (L-type Ca2+ channel blocker) restored neurite outgrowth inhibited by GPR143 overexpression to control levels, but had no effect in GPR143-knockdown cells. GPR143 overexpression and knockdown in PC12 cells; pharmacological inhibition with nifedipine, cilnidipine, flunarizine; neurite outgrowth quantification Journal of pharmacological sciences Medium 39068034
2022 L-DOPA promotes hippocampal neurogenesis through GPR143 in a dopamine-independent manner. L-DOPA at concentrations below those needed for dopamine signaling promoted neural stem/progenitor cell proliferation in wild-type but not Gpr143-/y mice under DOPA decarboxylase inhibition. Gpr143-/y mice show reduced hippocampal neurogenesis and increased depression-like behavior, rescued by re-expression of GPR143 in the dentate gyrus. Gpr143 knockout mice; DOPA decarboxylase inhibition; bromodeoxyuridine proliferation assay; viral re-expression of GPR143 in dentate gyrus; behavioral depression assays Stem cells High 35257172
2024 GPR143 oppositely regulates the two isoforms of the dopamine D2 receptor: it potentiates D2L (postsynaptic) function while suppressing D2S (presynaptic autoreceptor) function, as shown by differential effects on quinpirole-induced GSK3β phosphorylation in cells co-expressing each isoform with GPR143. CHO cell co-expression of GPR143 with D2L or D2S; GSK3β phosphorylation assay; dopamine release measurement (in vivo microdialysis); DA neuron-specific Gpr143 knockout (Dat-cre;Gpr143flox/y); haloperidol-induced catalepsy assay Journal of pharmacological sciences Medium 39179337
2021 GPR143 (Gpr143) is involved in pulmonary artery vasoconstriction by coupling with adrenergic α1 receptor (ADRA1): L-DOPA pretreatment enhanced phenylephrine-induced vasoconstriction in wild-type but not Gpr143-/y rat pulmonary arteries. Gpr143-/y rats showed attenuated right ventricular systolic pressure in a monocrotaline-induced pulmonary hypertension model. Gpr143 gene-deficient rat generation; isolated pulmonary artery contractility assay; monocrotaline-induced PH model; right ventricular pressure measurement; pulmonary artery smooth muscle cell migration and proliferation assays Journal of pharmacological sciences Medium 35063136
2016 Negative result: L-DOPA-induced ptosis in mice is GPR143-independent, as Gpr143-deficient mice showed ptosis to a similar extent as wild-type mice following L-DOPA administration under DOPA decarboxylase inhibition. Behavioral assay (ptosis scoring) in Gpr143-deficient and wild-type mice with DOPA decarboxylase inhibitor; dose-response analysis Journal of pharmacological sciences Medium 27622543

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 L-DOPA is an endogenous ligand for OA1. PLoS biology 158 18828673
2023 GPR143 controls ESCRT-dependent exosome biogenesis and promotes cancer metastasis. Developmental cell 137 36800996
2018 Cathelicidin-OA1, a novel antioxidant peptide identified from an amphibian, accelerates skin wound healing. Scientific reports 101 29343843
1995 Analysis of the OA1 gene reveals mutations in only one-third of patients with X-linked ocular albinism. Human molecular genetics 87 8634705
1999 X-linked late-onset sensorineural deafness caused by a deletion involving OA1 and a novel gene containing WD-40 repeats. American journal of human genetics 83 10330347
2000 Oa1 knock-out: new insights on the pathogenesis of ocular albinism type 1. Human molecular genetics 77 11092754
2009 The ocular albinism type 1 (OA1) G-protein-coupled receptor functions with MART-1 at early stages of melanogenesis to control melanosome identity and composition. Human molecular genetics 76 19717472
2000 Defective intracellular transport and processing of OA1 is a major cause of ocular albinism type 1. Human molecular genetics 65 11115845
1998 OA1 mutations and deletions in X-linked ocular albinism. American journal of human genetics 56 9529334
2005 The ocular albinism type 1 (OA1) gene controls melanosome maturation and size. Investigative ophthalmology & visual science 52 16303920
1993 The genes for X-linked ocular albinism (OA1) and microphthalmia with linear skin defects (MLS): cloning and characterization of the critical regions. Human molecular genetics 52 8364577
2015 Regulation of melanosome number, shape and movement in the zebrafish retinal pigment epithelium by OA1 and PMEL. Journal of cell science 48 25690007
2007 Identification of a novel GPR143 mutation in a large Chinese family with congenital nystagmus as the most prominent and consistent manifestation. Journal of human genetics 48 17516023
2005 The ocular albinism type 1 (OA1) protein and the evidence for an intracellular signal transduction system involved in melanosome biogenesis. Pigment cell research 45 16029416
2011 Screening of TYR, OCA2, GPR143, and MC1R in patients with congenital nystagmus, macular hypoplasia, and fundus hypopigmentation indicating albinism. Molecular vision 42 21541274
2006 The melanosomal/lysosomal protein OA1 has properties of a G protein-coupled receptor. Pigment cell research 40 16524428
2006 An unconventional dileucine-based motif and a novel cytosolic motif are required for the lysosomal and melanosomal targeting of OA1. Journal of cell science 38 16621890
2006 Aberrant splicing in the ocular albinism type 1 gene (OA1/GPR143) is corrected in vitro by morpholino antisense oligonucleotides. Human mutation 37 16550551
2018 Pigmentation and vision: Is GPR143 in control? Journal of neuroscience research 35 29761529
2002 New insights into ocular albinism type 1 (OA1): Mutations and polymorphisms of the OA1 gene. Human mutation 35 11793467
2001 Deletion in the OA1 gene in a family with congenital X linked nystagmus. The British journal of ophthalmology 35 11520764
2000 Expression pattern of the ocular albinism type 1 (Oa1) gene in the murine retinal pigment epithelium. Investigative ophthalmology & visual science 35 11095635
2016 Roles of OA1 octopamine receptor and Dop1 dopamine receptor in mediating appetitive and aversive reinforcement revealed by RNAi studies. Scientific reports 34 27412401
2013 Expression of OA1 limits the fusion of a subset of MVBs with lysosomes - a mechanism potentially involved in the initial biogenesis of melanosomes. Journal of cell science 34 24006264
2011 The ocular albinism type 1 (OA1) GPCR is ubiquitinated and its traffic requires endosomal sorting complex responsible for transport (ESCRT) function. Proceedings of the National Academy of Sciences of the United States of America 31 21730137
2008 Involvement of OA1, an intracellular GPCR, and G alpha i3, its binding protein, in melanosomal biogenesis and optic pathway formation. Investigative ophthalmology & visual science 28 18378571
2001 Diverse prevalence of large deletions within the OA1 gene in ocular albinism type 1 patients from Europe and North America. Human genetics 28 11214907
1996 Cloning of the murine homolog of the ocular albinism type 1 (OA1) gene: sequence, genomic structure, and expression analysis in pigment cells. Genome research 28 8889556
2019 l-DOPA and Its Receptor GPR143: Implications for Pathogenesis and Therapy in Parkinson's Disease. Frontiers in pharmacology 27 31632270
2015 Expression of ocular albinism 1 (OA1), 3, 4- dihydroxy- L-phenylalanine (DOPA) receptor, in both neuronal and non-neuronal organs. Brain research 26 25601010
2015 Deep intronic GPR143 mutation in a Japanese family with ocular albinism. Scientific reports 25 26061757
2014 The protein Ocular albinism 1 is the orphan GPCR GPR143 and mediates depressor and bradycardic responses to DOPA in the nucleus tractus solitarii. British journal of pharmacology 25 24117106
2014 Melanosome-autonomous regulation of size and number: the OA1 receptor sustains PMEL expression. Pigment cell & melanoma research 23 24650003
2008 Identification of a novel GPR143 deletion in a Chinese family with X-linked congenital nystagmus. Molecular vision 23 18523664
1996 Isolation and characterization of a mouse homolog of the X-linked ocular albinism (OA1) gene. Genomics 22 8921399
2008 Novel GPR143 mutations and clinical characteristics in six Chinese families with X-linked ocular albinism. Molecular vision 21 18978956
2003 Normal tissue depresses while tumor tissue enhances human T cell responses in vivo to a novel self/tumor melanoma antigen, OA1. Journal of immunology (Baltimore, Md. : 1950) 21 12538723
2015 GPR143 Gene Mutations in Five Chinese Families with X-linked Congenital Nystagmus. Scientific reports 20 26160353
1996 Mental retardation in a boy with an interstitial deletion at Xp22.3 involving STS, KAL1, and OA1: implication for the MRX locus. American journal of medical genetics 20 8870926
2003 Identification of three novel OA1 gene mutations identified in three families misdiagnosed with congenital nystagmus and carrier status determination by real-time quantitative PCR assay. BMC genetics 19 12515581
2007 The ocular albinism type 1 gene product, OA1, spans intracellular membranes 7 times. Experimental eye research 17 17920058
2011 Specific interaction of Gαi3 with the Oa1 G-protein coupled receptor controls the size and density of melanosomes in retinal pigment epithelium. PloS one 16 21931697
2009 Iris hyperpigmentation in a Chinese family with ocular albinism and the GPR143 mutation. American journal of medical genetics. Part A 16 19610097
1997 Clinical and molecular characterization of a family affected with X-linked ocular albinism (OA1). Ophthalmic genetics 16 9457748
1990 Localization of the X-linked ocular albinism gene (OA1) between DXS278/DXS237 and DXS143/DXS16 by linkage analysis. Ophthalmic paediatrics and genetics 16 2280973
2009 A novel GPR143 duplication mutation in a Chinese family with X-linked congenital nystagmus. Molecular vision 14 19390656
2007 A male infant with a 9.6 Mb terminal Xp deletion including the OA1 locus: Limit of viability of Xp deletions in males. American journal of medical genetics. Part A 14 17163525
2011 A novel GPR143 splicing mutation in a Chinese family with X-linked congenital nystagmus. Molecular vision 13 21423867
2006 Eight previously unidentified mutations found in the OA1 ocular albinism gene. BMC medical genetics 13 16646960
2020 Genetic associations of single nucleotide polymorphisms in the l-DOPA receptor (GPR143) gene with severity of nicotine dependence in Japanese individuals, and attenuation of nicotine reinforcement in Gpr143 gene-deficient mice. Journal of pharmacological sciences 12 32763057
2012 A case of 9.7 Mb terminal Xp deletion including OA1 locus associated with contiguous gene syndrome. Journal of Korean medical science 12 23091330
2023 Coupling between GPR143 and dopamine D2 receptor is required for selective potentiation of dopamine D2 receptor function by L-3,4-dihydroxyphenylalanine in the dorsal striatum. Journal of neurochemistry 11 36807226
2015 Role of ocular albinism type 1 (OA1) GPCR in Asian gypsy moth development and transcriptional expression of heat-shock protein genes. Pesticide biochemistry and physiology 11 26778432
2012 A novel nonsense mutation of the GPR143 gene identified in a Chinese pedigree with ocular albinism. PloS one 11 22916221
2003 Mutational analysis of the OA1 gene in ocular albinism. Ophthalmic genetics 11 12868035
2023 Investigation of GPR143 as a promising novel marker for the progression of skin cutaneous melanoma through bioinformatic analyses and cell experiments. Apoptosis : an international journal on programmed cell death 10 37945816
2019 GPR143 Signaling and Retinal Degeneration. Advances in experimental medicine and biology 10 31884582
2014 Localization of ocular albinism-1 gene product GPR143 in the rat central nervous system. Neuroscience research 10 25108060
2011 Structural insights into human GPCR protein OA1: a computational perspective. Journal of molecular modeling 10 21938455
2022 L-DOPA-Induced Neurogenesis in the Hippocampus Is Mediated Through GPR143, a Distinct Mechanism of Dopamine. Stem cells (Dayton, Ohio) 9 35257172
2012 Melanoregulin, product of the dsu locus, links the BLOC-pathway and OA1 in organelle biogenesis. PloS one 9 22984402
2006 Scanning the ocular albinism 1 (OA1) gene for polymorphisms in congenital nystagmus by DHPLC. Ophthalmic genetics 8 16754205
2024 Enhancement of Haloperidol-Induced Catalepsy by GPR143, an L-Dopa Receptor, in Striatal Cholinergic Interneurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 7 38286627
2017 GPR143 mutations in Chinese patients with ocular albinism type 1. Molecular medicine reports 7 28339057
2016 Simultaneous Expression of ABCA4 and GPR143 Mutations: A Complex Phenotypic Manifestation. Investigative ophthalmology & visual science 7 27367509
2014 Macular optical coherence tomography findings and GPR143 mutations in patients with ocular albinism. International ophthalmology 7 24526317
2013 A constitutively active Gαi3 protein corrects the abnormal retinal pigment epithelium phenotype of Oa1-/- mice. PloS one 7 24098784
2002 Diagnostic DNA testing for X-linked ocular albinism (OA1) with a hierarchical mutation screening protocol. Genetic testing 7 12180081
2022 CRISPR-AsCas12a Efficiently Corrects a GPR143 Intronic Mutation in Induced Pluripotent Stem Cells from an Ocular Albinism Patient. The CRISPR journal 6 35686978
2019 Evaluation of the iris thickness changes for the Chinese families with GPR143 gene mutations. Experimental eye research 6 31574285
2019 A novel GPR143 mutation in a Chinese family with X‑linked ocular albinism type 1. Molecular medicine reports 6 31746431
2018 Identification of a novel GPR143 mutation in X-linked ocular albinism with marked intrafamilial phenotypic variability. Journal of genetics 6 30555098
2013 A novel splicing site mutation of the GPR143 gene in a Chinese X-linked ocular albinism pedigree. Genetics and molecular research : GMR 6 24301936
2012 GPR143 gene mutation analysis in pediatric patients with albinism. Ophthalmic genetics 6 22486324
2005 Abnormal crossing of the optic fibres shown by evoked magnetic fields in patients with ocular albinism with a novel mutation in the OA1 gene. The British journal of ophthalmology 6 15965158
2024 L-DOPA Promotes Functional Proliferation Through GPR143, Specific L-DOPA Receptor of Astrocytes. ACS chemical neuroscience 5 39509688
2021 GPR143 genotypic and ocular phenotypic characterisation in a Chinese cohort with ocular albinism. Ophthalmic genetics 5 34346269
2022 Macular Findings in Carriers of Ocular Albinism With a Novel GPR143 Mutation. Ophthalmic surgery, lasers & imaging retina 4 35951714
2021 Identification of a novel GPR143 mutation in a large Chinese family with isolated foveal hypoplasia. BMC ophthalmology 4 33785018
2021 Right ventricular overloading is attenuated in monocrotaline-induced pulmonary hypertension model rats with a disrupted Gpr143 gene, the gene that encodes the 3,4-l-dihydroxyphenyalanine (l-DOPA) receptor. Journal of pharmacological sciences 4 35063136
2020 Distribution of mRNA for GPR143, a receptor of 3,4-L-dihydroxyphenylalanine, and of immunoreactivities for nicotinic acetylcholine receptors in the nigrostriatal and mesolimbic regions. Neuroscience research 4 32896531
2019 Overexpression of the gene product of ocular albinism 1 (GPR143/OA1) but not its mutant forms inhibits neurite outgrowth in PC12 cells. Journal of pharmacological sciences 4 31606330
2018 Generation of a human Ocular Albinism type 1 iPSC line, SEIi001-A, with a mutation in GPR143. Stem cell research 4 30513407
2018 Immunoreactivity of a G protein-coupled l-DOPA receptor GPR143, in Lewy bodies. Neuroscience research 4 30590075
2016 l-3,4-Dihydroxyphenylalanine induces ptosis through a GPR143-independent mechanism in mice. Journal of pharmacological sciences 4 27622543
2023 Mutation of GPR143 Associated With Ocular Albinism Type 1, Intellectual Disability, and Schizophrenia: The Complex Biological and Social Interactions Between Genetic Syndromes and Mental Illness. Journal of psychiatric practice 3 36649556
2021 Blue Cone Monochromatism with Foveal Hypoplasia Caused by the Concomitant Effect of Variants in OPN1LW/OPN1MW and GPR143 Genes. International journal of molecular sciences 3 34445325
2017 A Novel Acetaldehyde Dehydrogenase with Salicylaldehyde Dehydrogenase Activity from Rhodococcus ruber Strain OA1. Current microbiology 3 28849423
2024 Opposite regulation by L-DOPA receptor GPR143 of the long and short forms of the dopamine D2 receptors. Journal of pharmacological sciences 2 39179337
2019 Ocular albinism with mutation in GPR143: Findings in wide-field autofluorescence and optical coherence tomography. Archivos de la Sociedad Espanola de Oftalmologia 2 31103373
2016 Expression and localization of GPR143 in sheep skin. Yi chuan = Hereditas 2 27733339
2010 Identification of a novel deletion in the OA1 gene: report of the first Spanish family with X-linked ocular albinism. Clinical & experimental ophthalmology 2 20649618
2009 GPR143 mutational analysis in two Italian families with X-linked ocular albinism. Genetic testing and molecular biomarkers 2 19604113
2026 Disruption of the l-DOPA Receptor Gpr143/OA1-Gene in Mice Creates a Unique Mixed Psychosis-Like Phenotype. Neuropsychopharmacology reports 1 41510670
2024 Differences of ocular oscillations and neuro-retinal structures in patients with nystagmus caused by GPR143 and FRMD7 gene variants. Indian journal of ophthalmology 1 38648460
2024 l-DOPA receptor GPR143 inhibits neurite outgrowth via L-type calcium channels in PC12 cells. Journal of pharmacological sciences 1 39068034
2023 Involvement of the L-DOPA receptor GPR143 in acute and chronic actions of methylphenidate. Journal of pharmacological sciences 1 37257945
2023 L-DOPA Receptor GPR143 Functionally Couples with Adrenergic α1B Receptor at the Second Transmembrane Interface. Biological & pharmaceutical bulletin 1 37394637
2023 GPR143 mutations in an X-linked infantile nystagmus syndrome cohort in Southeast China. Molecular vision 1 38222445
1995 Intragenic TaqI restriction fragment length polymorphism (RFLP) in CICN4, between the loci for X-linked ocular albinism (OA1) and microphthalmia with linear skin defects syndrome (MLS). Human genetics 1 7759088

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