| 2013 |
GPR37L1 is activated by prosaptide (active fragment of prosaposin), which promotes receptor endocytosis, stimulates ERK phosphorylation in a pertussis toxin-sensitive manner, stimulates 35S-GTPγS binding, and inhibits forskolin-stimulated cAMP production, indicating Gi-coupled signaling. |
Transfected cell signaling assays (ERK phosphorylation, 35S-GTPγS binding, cAMP measurement), endocytosis assays, siRNA knockdown with oxidative stress protection readout |
Proceedings of the National Academy of Sciences of the United States of America |
High |
23690594
|
| 2013 |
GPR37L1 is localized to primary cilium membranes of Bergmann glia astrocytes in the cerebellum and physically interacts and colocalizes with the Sonic Hedgehog primary receptor Patched 1 (Ptch1); Gpr37l1 knockout results in premature downregulation of granule neuron precursor proliferation and precocious Bergmann glia and Purkinje neuron maturation, indicating GPR37L1 participates in postnatal cerebellar development by modulating the Shh pathway. |
Gpr37l1 knockout mice phenotypic analysis, colocalization/co-immunoprecipitation assays with Ptch1, primary cilium localization by specific assays |
Proceedings of the National Academy of Sciences of the United States of America |
High |
24062445
|
| 2016 |
GPR37L1 is constitutively active and couples to Gαs when heterologously expressed; the N-terminus is necessary for this constitutive activity; ADAM metalloprotease-mediated cleavage of the N-terminus renders the receptor inactive; the cleaved, inactive form predominates in rodent cerebellum. NOTE: This paper was retracted. |
cAMP accumulation assays in transfected cells and cerebellar slice preparations from wild-type vs. GPR37L1-null mice, ADAM inhibitor pharmacology, N-terminus deletion mutant analysis |
Science signaling |
Low |
27072655
|
| 2018 |
GPR37L1 mediates neuroprotective effects of TX14(A) (prosaptide/Saposin C fragment) in astrocytes, at least partially through Gi proteins and the cAMP-PKA axis, protecting neurons from oxidative stress; heterologous expression in HEK293 cells yields non-functional receptors that do not respond to TX14(A), suggesting a cell-context requirement. |
Primary astrocyte cultures, oxidative stress protection assay, pharmacological inhibition of Gi proteins (pertussis toxin), cAMP-PKA pathway inhibitors, comparison of HEK293 vs. native astrocyte expression systems |
Glia |
Medium |
30260505
|
| 2018 |
GPR37L1 deletion causes female-specific increase in systolic, diastolic, and mean arterial blood pressure, while male GPR37L1-null mice develop exacerbated left ventricular hypertrophy upon angiotensin II challenge. GPR37L1 protein is abundant in the brain but undetectable in heart and kidney, indicating cardiovascular regulation occurs centrally. |
GPR37L1 knockout mice (C57BL/6J background), radiotelemetric blood pressure measurement, angiotensin II infusion challenge, immunoblotting of tissue expression, β-galactosidase reporter immunohistochemistry |
Biology of sex differences |
Medium |
29625592
|
| 2018 |
GPR37L1 interacts with the short isoform of dopamine D2 receptor (D2R) in live cells, as detected by fluorescence cross-correlation spectroscopy (FCCS); this interaction was not modulated by 4-PBA or pramipexole treatment (unlike GPR37–D2R interaction). |
Fluorescence cross-correlation spectroscopy (FCCS) in live N2a cells |
Neuropharmacology |
Medium |
30423289
|
| 2020 |
GPR37L1 N-terminus is proteolytically cleaved by matrix metalloproteases/ADAMs at a site between residues 105–122; the larger cell-surface species is N-glycosylated at Asn105; wild-type GPR37L1 (but not the Δ122 truncation mutant) constitutively couples to Gαs (and Gα16) chimeras in yeast; the cleaved, inactive species predominates in vivo and in cerebellar slice preparations. |
Heterologous expression in HEK293 and U87 cells, ADAM/MMP pharmacological inhibitors, serial N-terminal truncation mutants, yeast G-protein chimera signaling assay, immunoblotting of rodent cerebellum and organotypic slice preparations |
Scientific reports |
High |
33203955
|
| 2020 |
In Bergmann glia primary cultures, Gpr37l1 loss-of-function increases cell proliferation, Ptch1 protein expression and internalization, intracellular cholesterol content, ciliary localization of Smoothened (Smo), and active Shh production, indicating GPR37L1–Ptch1 interactions regulate Ptch1 internalization/trafficking and downstream Shh mitogenic signaling. |
Primary cerebellar astrocyte cultures from wild-type and Gpr37l1-/- pups, immunofluorescence, proliferation assays, cholesterol measurement, prosaptide ligand treatment of wild-type cells |
Journal of neuroscience research |
Medium |
33350496
|
| 2021 |
GPR37L1 directly interacts with MLC proteins (MLC1 and GlialCAM) in brain astrocytes; Gpr37l1 inactivation in mice upregulates MLC proteins without altering their localization; the interaction is dynamically regulated by changes in osmolarity or potassium concentration. |
GlialCAM interactome proteomics, co-immunoprecipitation validation, immunohistochemistry in Gpr37l1-/- mice, osmolarity/K+ challenge assays |
Human molecular genetics |
Medium |
34100078
|
| 2021 |
GPR37L1 and GPR37 form homo- and heterodimers in live N2a cells; GPR37L1 does not aggregate in the cytoplasm (unlike GPR37 which forms cytoplasmic multimers reversible by Parkin overexpression). |
Fluorescence Cross-Correlation Spectroscopy (FCCS), Förster Resonance Energy Transfer (FRET), and Fluorescence Lifetime Imaging Microscopy (FLIM) in live N2a cells |
FASEB journal |
Medium |
34822195
|
| 2024 |
GPR37L1 in satellite glial cells (SGCs) of dorsal root ganglia serves as a receptor for the pro-resolving lipid mediator maresin 1 (MaR1); upon activation, GPR37L1 enhances surface expression and function of potassium channels KCNJ10 (Kir4.1) and KCNJ3 (Kir3.1) in SGCs, increasing potassium influx; GPR37L1 loss impairs resolution of neuropathic pain while overexpression reverses it. |
Transgenic Gpr37l1-/- and overexpression mice, electrophysiology (potassium channel function), surface biotinylation (channel surface expression), GPR37L1 ligand binding assays with MaR1, neuropathic pain behavioral assays (PTX/STZ models) |
The Journal of clinical investigation |
High |
38530364
|
| 2025 |
GPR37L1 activation by maresin 1 (MaR1) in spinal cord dorsal horn astrocytes increases glutamate transporter 1 (GLT-1) activity and reduces spinal EPSCs; Gpr37l1 knockdown in SDH astrocytes induces astrogliosis and pain hypersensitivity; Gpr37l1-/- mice fail to recover from neuropathic pain; selective Gpr37l1 overexpression in SDH astrocytes reverses neuropathic pain and astrogliosis after nerve injury. |
Gpr37l1-/- mice, AAV-mediated Gpr37l1 knockdown/overexpression in spinal cord astrocytes, GLT-1 functional assay, spinal EPSC electrophysiology, nerve injury neuropathic pain behavioral model |
Neuron |
High |
39952243
|
| 2024 |
Rare GPR37L1 variants exhibit varying abilities to reduce cAMP levels, activate MAPK/ERK signaling, and upregulate receptor expression in response to prosaptide TX14(A); GPR37L1 knockout or expression of certain rare variants alters cellular cholesterol levels, which are also acutely regulated by TX14(A) via the MAPK pathway. |
Functional signaling assays in SK-N-MC cells (cAMP, MAPK), cholesterol quantification, GPR37L1 KO cell line, rare variant expression constructs |
The Journal of neuroscience |
Medium |
38569927
|
| 2017 |
Complete loss of Gpr37l1 function in mice results in increased seizure susceptibility; combined deletion of Gpr37l1 and Gpr37 results in an even more dramatic increase in seizure vulnerability, indicating additive/epistatic interaction between the two receptors in seizure threshold control. The K349N human variant did not grossly alter receptor expression, surface trafficking, or constitutive signaling in transfected cells. |
Gpr37l1-/- and Gpr37-/- single and double knockout mice, seizure susceptibility assays; transfected cell expression and signaling assays for K349N variant |
Neurobiology of disease |
Medium |
28688853
|
| 2020 |
GPR37L1-null mice of both sexes exhibit attenuated depressor responses to ganglionic blockade with pentolinium, indicating GPR37L1 is involved in maintaining sympathetic vasomotor tone; female GPR37L1-/- mice show reduced cardiac vagal drive (reduced heart rate spectral power 0.5–3 Hz) and attenuated cardiovascular reactivity to aversive environmental stimuli. |
Radiotelemetric blood pressure and heart rate measurement, power spectral analysis, pharmacological ganglionic blockade (pentolinium), behavioral stress tests in Gpr37l1-/- mice |
Frontiers in pharmacology |
Medium |
33633567
|
| 2018 |
Genetic ablation of Gpr37l1 in Ptch1+/- mice delays medulloblastoma tumor onset and decreases incidence of aggressive tumor types; Gpr37l1-/-;Ptch1+/- pups show reduced granule cell precursor proliferation, thinner EGL, and precocious elevated Wnt3 expression compared to Ptch1+/- single mutants, indicating GPR37L1 modulates Shh-Ptch1-Smo mitogenic signaling in medulloblastoma pathogenesis. |
Double-mutant mouse model (Gpr37l1-/-;Ptch1+/-), natural history tumor analysis, histology of EGL, immunostaining for Wnt3 expression |
Experimental neurology |
Medium |
30452905
|
| 2023 |
Loss of GPR37L1 in mice causes cortical astrocytes to express lower levels of mature astrocytic genes, exhibit shorter total process length, reduced morphological complexity, and increased spacing between astrocytes in the cortex, establishing GPR37L1 as a regulator of astrocyte maturation and morphological organization during development. |
RNA-seq of immunopanned cortical astrocytes from P7 Gpr37l1-/- vs. WT mice, immunohistochemistry of astrocyte morphology in cortex |
Glia |
Medium |
37029775
|