Affinage

GPR161

G-protein coupled receptor 161 · UniProt Q8N6U8

Length
529 aa
Mass
58.6 kDa
Annotated
2026-04-28
39 papers in source corpus 18 papers cited in narrative 18 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GPR161 is a constitutively active orphan G-protein-coupled receptor that localizes to primary cilia and functions as a central negative regulator of Hedgehog (Hh) signaling by coupling to Gαs to elevate cAMP and by directly scaffolding type I PKA via an A-kinase anchoring protein (AKAP) motif in its C-terminal tail, thereby promoting GLI3 processing to its repressor form (PMID:23332756, PMID:27357676, PMID:38326651). A cryo-EM structure reveals that a sterol bound at transmembrane helices 6/7 stabilizes the Gs-coupling conformation, while the PKA-binding C-terminal domain—rather than sterol-dependent cAMP production—is the critical determinant for suppressing GLI2 accumulation in cilia (PMID:38326651). Ciliary trafficking of GPR161 depends on Tulp3/IFT-A for import (PMID:23332756), and Hh-triggered export requires GRK2 phosphorylation, β-arrestin recruitment, and coupling to the BBSome–IFT machinery for clathrin-mediated removal (PMID:27002170, PMID:40384633). Loss of Gpr161 causes cilium-dependent ectopic Hh pathway activation leading to neural tube defects, medulloblastoma, polydactyly, and skeletal patterning abnormalities in mice, and rare GPR161 variants have been identified in human spina bifida patients (PMID:29386106, PMID:29222391, PMID:30256984).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 2008 Medium

    Identification of a C-terminal truncation mutation in Gpr161 (vacuolated lens allele) established that the receptor's C-terminal tail is essential for endocytic trafficking and that its loss causes neural tube defects and cataracts, providing the first link between GPR161 and developmental signaling.

    Evidence Positional cloning and endocytosis assays in mutant mouse cells

    PMID:18250320

    Open questions at the time
    • No pathway mechanism identified
    • No ciliary localization reported
    • Single mouse allele
  2. 2013 High

    The foundational mechanistic framework was established: GPR161 localizes to primary cilia via Tulp3/IFT-A, constitutively activates cAMP/PKA to promote Gli3 repressor formation, and is removed from cilia upon Shh stimulation—resolving how the cilium suppresses Hh signaling in the absence of ligand.

    Evidence Mouse Gpr161 knockout, cAMP reporter assays, Gli3 processing immunoblots, ciliary immunofluorescence, epistasis with IFT-A/Tulp3 mutants

    PMID:23332756

    Open questions at the time
    • Mechanism of ciliary exit unknown
    • Coupling to PKA not mapped to a direct binding interface
    • No structural information on receptor
  3. 2015 Medium

    A hypomorphic Gpr161 allele revealed Shh-independent regulation of retinoic acid and Wnt pathway gene expression during neurulation, suggesting broader signaling roles for GPR161 beyond Hedgehog repression.

    Evidence QRT-PCR, in situ hybridization, retinoic acid rescue of neural tube defects in Gpr161 hypomorphic mice

    PMID:25753732

    Open questions at the time
    • Pathway connection to RA and Wnt is indirect
    • Not confirmed in independent genetic backgrounds
    • Mechanism linking cAMP to Wnt/RA regulation unclear
  4. 2016 High

    Two key mechanisms were resolved in parallel: (1) Shh-induced ciliary removal proceeds through GRK2 phosphorylation of GPR161, β-arrestin recruitment, and clathrin-mediated endocytosis; (2) GPR161 directly binds type I PKA regulatory subunits via a C-terminal AKAP motif, compartmentalizing PKA to cilia and the plasma membrane.

    Evidence β-arrestin recruitment and clathrin inhibition assays with live-cell imaging; phosphoproteomics, direct binding assays, AKAP domain mutagenesis, zebrafish in vivo rescue

    PMID:27002170 PMID:27357676

    Open questions at the time
    • Role of BBSome in β-arrestin-mediated export not yet defined
    • Relative contributions of cAMP production vs. PKA anchoring to Gli repression unresolved
  5. 2018 High

    Conditional knockouts demonstrated that Gpr161 loss causes cilium-dependent tissue-specific Hh pathway hyperactivation, driving medulloblastoma from cerebellar granule cell progenitors and limb/skeletal patterning defects—establishing GPR161 as a bona fide Hh pathway tumor suppressor.

    Evidence Cell-type-specific conditional knockout mice with genetic cilia ablation epistasis, histological and molecular pathway analysis

    PMID:29222391 PMID:29386106

    Open questions at the time
    • Human tumor suppressor role not validated by patient mutation data at this point
    • Hh-independent functions in these tissues not tested
  6. 2019 High

    The IFT-B–BBSome connection required for GPR161 ciliary export was mapped: IFT38 directly binds BBSome subunits, and disrupting this interaction traps GPR161 in cilia. Separately, rare GPR161 variants in human spina bifida patients were shown to mislocalize and dominantly disrupt Shh signaling.

    Evidence IFT38 knockout + rescue with BBSome-interaction-deficient mutant; Sanger sequencing of spina bifida patients with in vitro functional characterization

    PMID:30256984 PMID:31471295

    Open questions at the time
    • Full reconstitution of the GPR161–β-arrestin–BBSome–IFT export complex not achieved
    • Spina bifida variants characterized in vitro only, lacking in vivo rescue
  7. 2021 High

    Separation-of-function studies dissected ciliary vs. extraciliary GPR161 roles: a ciliary-localization-defective but cAMP-competent knock-in showed that the ciliary pool specifically controls Gli3 repressor thresholds in the neural tube, while PKA feedback phosphorylation of GPR161 fine-tunes its own ciliary retention and Hh sensitivity.

    Evidence Knock-in mouse allelic series with tissue-level pathway readouts; zebrafish transgenic rescue with phospho-deficient GPR161 mutants and BRET-based Gαs coupling

    PMID:33450431 PMID:33531430 PMID:34346313

    Open questions at the time
    • Extraciliary GPR161 function mechanism remains molecularly undefined
    • Mechanoresponsive role via AC6 seen in MSCs not validated in other cell types
  8. 2024 High

    Cryo-EM structure of GPR161–Gs resolved the molecular basis of constitutive activity: ECL2 occupies the orthosteric pocket, a sterol at TM6/7 stabilizes the active conformation for Gs coupling, and critically, the C-terminal PKA-binding site—not sterol-dependent cAMP—is the essential feature for suppressing GLI2 ciliary accumulation, separating cAMP production from PKA anchoring as distinct functional outputs.

    Evidence Cryo-EM structure, sterol-binding and PKA-binding site mutagenesis, cAMP and GLI2 ciliary accumulation assays

    PMID:38326651

    Open questions at the time
    • Endogenous sterol ligand identity not confirmed
    • No structure of inactive or β-arrestin-bound state
    • How PKA anchoring mechanistically suppresses GLI2 at cilia is unresolved
  9. 2025 High

    The complete β-arrestin–BBSome export pathway was reconstituted: β-arrestins are required for GPR161 ciliary exit, activation-mimetic β-arrestin mutants constitutively interact with the BBSome and GPR161 to drive export, and GRK2 phosphorylation initiates this cascade. Separately, GPR161 was shown to function as a ciliary mechanosensor whose helix 8 mediates shear-stress responsiveness to drive NDE1 phosphorylation and saltatory neuronal migration.

    Evidence ARRB1/ARRB2 double-KO cells with activation-mimetic rescue and co-IP; microfluidic shear-stress assays with helix 8 mutagenesis and NDE1 phosphorylation analysis

    PMID:40384633 PMID:40737401

    Open questions at the time
    • Structural basis of β-arrestin–BBSome interaction unknown
    • Helix 8 mechanosensing mechanism not structurally defined
    • In vivo relevance of mechanosensing for brain development needs confirmation
  10. 2025 High

    GLI3 repressor was identified as the essential effector of GPR161-dependent cranial neural tube closure: GLI3R expression, but not GLI2 loss, rescues exencephaly in Gpr161 knockouts, with GLI3R restricting forebrain floor plate expansion and mediating apical constriction for neural fold closure.

    Evidence Gpr161 allelic series × GLI effector mutant epistasis, non-ciliary knock-in, in toto live imaging

    PMID:41417007

    Open questions at the time
    • Molecular mechanism linking GLI3R to apical constriction machinery unknown
    • Whether this mechanism operates in human cranial closure untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include the identity of the endogenous sterol or lipid ligand that activates GPR161, the structural basis of the inactive and β-arrestin-bound receptor states, how PKA anchoring at cilia mechanistically controls GLI2 accumulation independently of cAMP, and the full extent of Hedgehog-independent GPR161 signaling roles (Wnt, RA, mTORC1).
  • Endogenous activating ligand unidentified
  • No inactive-state or arrestin-bound structure
  • PKA-anchoring-to-GLI2 mechanism unresolved
  • Hh-independent roles lack in vivo mechanistic validation

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 3 GO:0140299 molecular sensor activity 2 GO:0060090 molecular adaptor activity 1
Localization
GO:0005929 cilium 6 GO:0005886 plasma membrane 2
Pathway
R-HSA-162582 Signal Transduction 6 R-HSA-1266738 Developmental Biology 4
Partners
ARRB2FUZGNASGRK2IFT38IQGAP1PRKAR1ATULP3
Complex memberships
GPR161–PKA-RI (AKAP complex)GPR161–β-arrestin–BBSome export complex

Evidence

Reading pass · 18 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2013 GPR161 localizes to primary cilia in a Tulp3/IFT-A-dependent manner and constitutively increases cAMP levels, promoting PKA-dependent processing of Gli3 to its repressor form, thereby repressing Sonic hedgehog (Shh) signaling. Shh signaling directs GPR161 internalization from cilia, preventing its activity. Mouse knockout, cAMP reporter assays, Gli3 processing immunoblots, ciliary localization by immunofluorescence, epistasis with IFT-A/Tulp3 mutants Cell High 23332756
2016 Shh pathway activation drives GPR161 removal from primary cilia in a two-step process: first, GRK2-mediated phosphorylation recruits β-arrestin to GPR161 (facilitated by ciliary Smoothened activation increasing GPR161-β-arrestin binding); second, clathrin-mediated endocytosis outside the cilium completes removal. β-arrestin recruitment assays, GRK2 inhibition/knockdown, clathrin inhibition, live-cell imaging, co-immunoprecipitation The Journal of cell biology High 27002170
2016 GPR161 functions as an A-kinase anchoring protein (AKAP) that directly binds type I PKA regulatory subunits (RI) via a hydrophobic interface in its cytoplasmic C-terminal tail. This binary complex compartmentalizes PKA to the plasma membrane and to primary cilia. GPR161 is itself a PKA phosphorylation target, and mutation of the PKA phosphorylation site affects its ciliary localization. Phosphoproteomics, cell-based protein-protein interaction reporters, direct binding assays, zebrafish in vivo rescue experiments, site-directed mutagenesis Proceedings of the National Academy of Sciences of the United States of America High 27357676
2014 GPR161 forms a signaling complex with β-arrestin 2 and IQGAP1 (a regulator of mTORC1 and E-cadherin). GPR161 overexpression activates mTORC1 signaling, decreases IQGAP1 phosphorylation, and promotes cell proliferation, migration, and intracellular accumulation of E-cadherin in mammary epithelial cells. Co-immunoprecipitation, knockdown/overexpression functional assays, 3D culture, signaling pathway analysis Proceedings of the National Academy of Sciences of the United States of America Medium 24599592
2008 A C-terminal truncation mutation in Gpr161 (vacuolated lens allele) reduces receptor-mediated endocytosis and causes neural tube defects and cataracts in mice, establishing the C-terminal tail as required for normal endocytic trafficking. Positional cloning, endocytosis assays in mutant cells, mouse genetic analysis Proceedings of the National Academy of Sciences of the United States of America Medium 18250320
2019 The IFT-B subunit IFT38 directly interacts with BBSome subunits BBS1, BBS2, and BBS9. This IFT-B–BBSome interaction is required for export of GPR161 from cilia upon Hedgehog signaling activation; cells expressing an IFT38 mutant that cannot bind the BBSome accumulate GPR161 within cilia. Visible immunoprecipitation assay, IFT38 knockout cell lines, rescue with wild-type vs. interaction-deficient IFT38 mutants, immunofluorescence Biology open High 31471295
2018 Gpr161 deletion in mouse neural stem cells or granule cell (GC) progenitors increases Shh pathway activity by restricting Gli3-mediated repression, causing excessive GC progenitor proliferation and medulloblastoma; the overproduction phenotype is cilium-dependent. Conditional knockout mouse models (neural stem cell- and GC progenitor-specific), cilium-dependency tested by genetic cilia ablation, pathway analysis Cell reports High 29386106
2018 Limb-specific deletion of Gpr161 causes premature expansion of Shh signaling and ectopic Shh-dependent patterning defects; loss of Gpr161 in chondrocytes prevents columnar differentiation and Ihh signaling. All limb and skeletal morphogenesis defects are suppressed in the absence of cilia, placing Gpr161 upstream of cilia-dependent hedgehog signaling in these tissues. Conditional knockout mice, genetic epistasis with cilia mutants, histological and molecular analysis of signaling Development (Cambridge, England) High 29222391
2021 A ciliary localization-defective but cAMP-signaling-competent knock-in variant of Gpr161 (Gpr161mut1) shows that ciliary and extraciliary pools of Gpr161 establish tissue-specific Gli repressor thresholds: loss of ciliary localization causes intermediate neural tube progenitor expansion (Gli3 repressor-dependent) but not the ventral-most Gli2 activator-dependent expansion seen in full knockouts. Polydactyly and midfacial widening result from loss of ciliary localization. Knock-in mouse engineering, conditional allele comparisons (KO vs. cilia-defective mutant), immunofluorescence, pathway target analysis eLife High 34346313
2024 Cryo-EM structure of active human GPR161 bound to heterotrimeric Gs revealed: (1) extracellular loop 2 occupies the canonical orthosteric ligand pocket; (2) a sterol binds adjacent to transmembrane helices 6 and 7 and stabilizes the Gs-coupling conformation—mutations preventing sterol binding suppress cAMP signaling but retain the ability to suppress GLI2 accumulation in cilia; (3) the PKA-binding site in the GPR161 C-terminus is critical for suppressing GLI2 ciliary accumulation. Cryo-EM structure determination, site-directed mutagenesis of sterol-binding site and PKA-binding site, cAMP assays, GLI2 ciliary accumulation assays Nature structural & molecular biology High 38326651
2021 PKA feedback phosphorylation of Gpr161 fine-tunes its ciliary localization and PKA activity. PKA phosphorylation-deficient Gpr161 shows increased sensitivity to Shh, resulting in excess high-level Hh target gene expression in zebrafish, demonstrating a feedback loop controlling Gpr161 activity. Zebrafish loss-of-function, transgenic rescue with phosphorylation-deficient Gpr161 mutants, BRET-based Gαs coupling assay, Hh target gene expression analysis Development (Cambridge, England) Medium 33531430
2019 Novel rare GPR161 variants identified in spina bifida patients mislocalize to primary cilia, dysregulate Shh and Wnt signaling, and inhibit cell proliferation in vitro, acting as dominant negatives. Sanger sequencing, in vitro ciliary localization by immunofluorescence, Shh/Wnt pathway reporter assays, cell proliferation assays Human molecular genetics Medium 30256984
2021 Gpr161 is a mechanoresponsive receptor in mesenchymal stem cells (MSCs) that localizes to the primary cilium and mediates fluid shear stress-induced cAMP signaling and osteogenesis through adenylyl cyclase 6 (AC6). Hh signaling downstream of this Gpr161-AC6-cAMP axis is required for loading-induced osteogenic differentiation. Fluid shear stress assay, siRNA knockdown of Gpr161, AC6, and IFT88, cAMP measurement, osteogenesis assays Bone Medium 33450431
2025 GPR161 acts as a mechanical sensor at the primary cilium with its helix 8 being essential for mechanosensitivity. Fluid shear stress activates GPR161, triggering a cAMP/PKA signaling cascade that phosphorylates NDE1 (a dynein complex regulator) and reorganizes microtubules to drive the saltatory migration of neurons. Ex vivo neuronal migration model, microfluidic assays, helix 8 mutagenesis, NDE1 phosphorylation analysis, live imaging Science advances Medium 40737401
2025 β-arrestins (ARRB1 and ARRB2) are required for GPR161 export from cilia. Activation-mimetic β-arrestin mutants interact with both the BBSome and ciliary GPR161 and cause constitutive GPR161 export. GRK2 phosphorylates GPR161 to recruit β-arrestins, which in their activated conformation interact with the BBSome to connect GPR161 to the IFT machinery for export. ARRB1/ARRB2 double-knockout cells, expression of activation-mimetic β-arrestin mutants, co-immunoprecipitation, IFT27/BBSome-KO analysis, immunofluorescence Journal of cell science High 40384633
2024 Fuz is genetically epistatic to Gpr161 in Shh signaling during mouse neural tube development. The Fuz protein biochemically interacts with GPR161, and Fuz regulates GPR161-mediated ciliary localization through a mechanism involving β-arrestin 2. Double-mutant epistasis in mice, co-immunoprecipitation, ciliary localization assays, β-arrestin 2 functional analysis Development (Cambridge, England) Medium 39369306
2025 Cranial neural tube closure requires GPR161 ciliary localization for GLI3 repressor (GLI3R) formation. Epistasis experiments show that Gli3R expression, but not Gli2 loss, rescues exencephaly in Gpr161 knockout mice. GLI3R restricts forebrain ventral floor plate expansion and mediates apical constriction in lateral midbrain neural folds prior to closure. Gpr161 mutant allelic series, genetic epistasis (Gpr161 KO × GLI effector mutants), non-ciliary Gpr161 knock-in, in toto live imaging Development (Cambridge, England) High 41417007
2015 In the context of a hypomorphic Gpr161 allele, Gpr161 regulates retinoic acid (RA) and canonical Wnt pathway gene expression during neurulation independently of severe Shh pathway effects. RA injection rescues Wnt markers and neural tube defects in Gpr161 hypomorphs. QRT-PCR, ISH, IHC, RA injection rescue experiments, modifier QTL analysis in mice Developmental biology Medium 25753732

Source papers

Stage 0 corpus · 39 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 The ciliary G-protein-coupled receptor Gpr161 negatively regulates the Sonic hedgehog pathway via cAMP signaling. Cell 402 23332756
2016 Smoothened determines β-arrestin-mediated removal of the G protein-coupled receptor Gpr161 from the primary cilium. The Journal of cell biology 118 27002170
2016 Gpr161 anchoring of PKA consolidates GPCR and cAMP signaling. Proceedings of the National Academy of Sciences of the United States of America 94 27357676
2014 G-protein-coupled receptor GPR161 is overexpressed in breast cancer and is a promoter of cell proliferation and invasion. Proceedings of the National Academy of Sciences of the United States of America 65 24599592
2008 The orphan G protein-coupled receptor, Gpr161, encodes the vacuolated lens locus and controls neurulation and lens development. Proceedings of the National Academy of Sciences of the United States of America 60 18250320
2019 Germline GPR161 Mutations Predispose to Pediatric Medulloblastoma. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 55 31609649
2015 Whole-exome sequencing identifies homozygous GPR161 mutation in a family with pituitary stalk interruption syndrome. The Journal of clinical endocrinology and metabolism 55 25322266
2018 The G protein-coupled receptor Gpr161 regulates forelimb formation, limb patterning and skeletal morphogenesis in a primary cilium-dependent manner. Development (Cambridge, England) 54 29222391
2018 Basal Suppression of the Sonic Hedgehog Pathway by the G-Protein-Coupled Receptor Gpr161 Restricts Medulloblastoma Pathogenesis. Cell reports 47 29386106
2019 Requirement of IFT-B-BBSome complex interaction in export of GPR161 from cilia. Biology open 41 31471295
2020 Hedgehog and Gpr161: Regulating cAMP Signaling in the Primary Cilium. Cells 34 31947770
2020 Enterotoxigenic Escherichia coli infection promotes enteric defensin expression via FOXO6-METTL3-m6A-GPR161 signalling axis. RNA biology 31 32914682
2019 Dominant negative GPR161 rare variants are risk factors of human spina bifida. Human molecular genetics 30 30256984
2019 Derepression of sonic hedgehog signaling upon Gpr161 deletion unravels forebrain and ventricular abnormalities. Developmental biology 29 30914320
2024 GPR161 structure uncovers the redundant role of sterol-regulated ciliary cAMP signaling in the Hedgehog pathway. Nature structural & molecular biology 28 38326651
2021 Ciliary and extraciliary Gpr161 pools repress hedgehog signaling in a tissue-specific manner. eLife 28 34346313
2015 The orphan GPCR, Gpr161, regulates the retinoic acid and canonical Wnt pathways during neurulation. Developmental biology 28 25753732
2021 Primary cilium-mediated MSC mechanotransduction is dependent on Gpr161 regulation of hedgehog signalling. Bone 21 33450431
2021 Feedback control of the Gpr161-Gαs-PKA axis contributes to basal Hedgehog repression in zebrafish. Development (Cambridge, England) 15 33531430
2021 Wnt1 Lineage Specific Deletion of Gpr161 Results in Embryonic Midbrain Malformation and Failure of Craniofacial Skeletal Development. Frontiers in genetics 13 34887903
2024 In vivo and in vitro anti-inflammation of Rhapontici Radix extract on mastitis via TMEM59 and GPR161. Journal of ethnopharmacology 11 38942158
2023 Primary cilia, A-kinase anchoring proteins and constitutive activity at the orphan G protein-coupled receptor GPR161: A tale about a tail. British journal of pharmacology 10 36772847
2009 Mucosal or systemic administration of rE2 glycoprotein antigen loaded PLGA microspheres. International journal of pharmaceutics 8 19429284
2023 Pax3 lineage-specific deletion of Gpr161 is associated with spinal neural tube and craniofacial malformations during embryonic development. Disease models & mechanisms 7 37885410
2022 Development of Highly Sensitive Sandwich ELISA for the Early-Phase Diagnosis of Chikungunya Virus Utilizing rE2-E1 Protein. Infection and drug resistance 5 35924014
2017 Suspension culture process for H9N2 avian influenza virus (strain Re-2). Archives of virology 5 28685290
2018 Selective Cleavage of C-O Bonds in Lignin Catalyzed by Rhenium(VII) Oxide (Re2 O7 ). ChemPlusChem 4 31950656
2015 Synthesis and X-ray crystal structure of the dirhenium complex Re2(i-C3H7COO)4Cl2 and its interactions with the DNA purine nucleobases. Journal of inorganic biochemistry 3 26315264
2025 β-Arrestin mediates the export of ciliary GPR161 but not Smoothened together with the BBSome and intraflagellar transport machinery. Journal of cell science 2 40384633
2025 GPR161 mechanosensitivity at the primary cilium drives neuronal saltatory migration. Science advances 2 40737401
2024 Linkage between Fuz and Gpr161 genes regulates sonic hedgehog signaling during mouse neural tube development. Development (Cambridge, England) 2 39369306
2023 GPR161 structure uncovers the redundant role of sterol-regulated ciliary cAMP signaling in the Hedgehog pathway. bioRxiv : the preprint server for biology 2 37292845
2025 GPR161-GLI3 repressor signaling at cilia directs apical constriction and cell fate during cranial neural tube closure. Development (Cambridge, England) 1 41417007
2024 The novel linkage between Fuz and Gpr161 genes regulates sonic hedgehog signaling during mouse embryonic development. bioRxiv : the preprint server for biology 1 38260275
2019 Identification and spatiotemporal expression of gpr161 genes in zebrafish. Gene 1 31884103
2026 Oncogenic GPR161 Drives Melanoma Proliferation and Metabolic Activity through TXNIP Inhibition. Journal of microbiology and biotechnology 0 41834581
2026 Expression Analysis of the orphan receptors GPR161, GPR132, GPR20, and GPR139 in patients with cervicitis and low-grade, and high-grade squamous intraepithelial lesions. Genetics and molecular biology 0 41915403
2025 Identification of novel interacting proteins of FUZ and GPR161. bioRxiv : the preprint server for biology 0 41000683
2023 Pax3 lineage-specific deletion of Gpr161 is associated with spinal neural tube and craniofacial malformations during embryonic development. bioRxiv : the preprint server for biology 0 37461574