| 1992 |
VILIP (VSNL1 ortholog in chicken) was identified as a neuronal EF-hand Ca2+-binding protein with four EF-hand motifs, showing 40-46% sequence identity to retinal calcium-binding proteins visinin and recoverin, and expressed widely in brain but not in liver, heart, or skeletal muscle. |
cDNA cloning, Northern analysis, in situ hybridization |
Brain research. Molecular brain research |
High |
1359372
|
| 1994 |
VILIP (VSNL1) binds only two active Ca2+/Mg2+ sites (not four), with Ca2+ affinity K'Ca of 1.0×10^6 M-1 and Mg2+ affinity K'Mg of 4.8×10^3 M-1; Ca2+ binding causes 20-30% increase in Trp fluorescence indicating conformational change; Mg2+ form resembles metal-free form unlike NCS-1. |
Flow dialysis (Ca2+ binding), equilibrium gel filtration (Mg2+ binding), Trp fluorescence spectroscopy, near UV difference spectra, DTNB thiol reactivity assay on recombinant proteins expressed in E. coli |
The Journal of biological chemistry |
High |
7806504
|
| 1996 |
VILIP (VSNL1) exists in cytoplasmic, membrane-associated, and cytoskeleton-associated pools; its association with the cytoskeletal fraction is Ca2+-dependent and mediated by direct interaction with actin, as Ca2+-loaded recombinant VILIP binds actin in overlay assay, β-actin co-immunoprecipitates with native VILIP from brain extracts in presence of Ca2+, and actin and VILIP co-localize in VILIP-transfected PC12 cells. |
Cell fractionation, actin overlay assay, co-immunoprecipitation, immunocytochemistry in transfected PC12 cells |
Biochemical and biophysical research communications |
High |
8780737
|
| 1997 |
VILIP-1 (VSNL1) increases β-adrenergic receptor-stimulated cAMP levels in C6 glioma cells, acting downstream of receptor and G protein (also stimulated by forskolin); this effect requires N-terminal myristoylation, as the myristoylation-deficient mutant reduces cAMP levels instead; myristoylated wild-type VILIP associates with membranes in a Ca2+-dependent manner (calcium-myristoyl switch) while the non-myristoylated mutant shows strongly reduced membrane association. |
Stable transfection in C6 glioma cells, cAMP assay, subcellular fractionation, site-directed mutagenesis of myristoylation site |
Journal of neurochemistry |
High |
9109541
|
| 1997 |
VILIP (VSNL1) is expressed in olfactory sensory cell cilia and dendritic knobs, and recombinant VILIP attenuates odorant-induced cAMP formation in olfactory cilia preparations in a Ca2+-dependent manner, likely by directly affecting adenylyl cyclase (also inhibits forskolin-induced cAMP formation), without interfering with receptor desensitization. |
Immunolocalization, in vitro cAMP assay with olfactory cilia preparations using recombinant VILIP |
European journal of cell biology |
Medium |
9157011
|
| 1997 |
Low-level expression of myristoylated wild-type VILIP in C6 cells elevates basal cAMP and induces astrocyte-like differentiation with increased GFAP expression; non-myristoylated VILIP mutant reduces cAMP and GFAP without inducing differentiated morphology, demonstrating myristoylation-dependent cAMP regulation drives differentiation. |
Stable transfection in C6 cells, cAMP measurement, immunostaining for GFAP, morphological analysis |
Neuroscience letters |
Medium |
9364517
|
| 1997 |
Wild-type VILIP in PC12 cells associates strongly with cell membranes (especially cell-cell contacts) in a Ca2+-dependent manner, whereas myristoylation-deficient VILIP distributes more evenly with much less membrane association, demonstrating the calcium-myristoyl switch as the primary but not sole determinant of membrane targeting. |
Stable transfection in PC12 cells, immunocytochemistry, subcellular fractionation and Western blot |
Neuroscience letters |
Medium |
9147390
|
| 1999 |
VILIP (VSNL1) contains a double-stranded RNA-binding domain and specifically binds dsRNA in a Ca2+-dependent manner as a single protein-RNA complex (Kd ~9×10^-6 M); VILIP specifically binds the 3'-UTR of the trkB neurotrophin receptor mRNA, suggesting a role in Ca2+-dependent regulation of localized mRNA in hippocampal dendrites. |
Mobility shift assay, RNA binding assay with recombinant VILIP, domain analysis |
The Journal of biological chemistry |
Medium |
10531361
|
| 2001 |
VILIP-1 (VSNL1) expression in PC12 cells enhances ionomycin-induced cytotoxicity and increases tau hyperphosphorylation compared to control or calbindin-D28K-transfected cells; co-expression of calbindin-D28K rescues VILIP-1-mediated cytotoxicity; VILIP-1 associates with amyloid plaques and extracellular tangles in Alzheimer's disease brains. |
Stable transfection of PC12 cells, cytotoxicity assays, tau phosphorylation immunoblot, immunohistochemistry in AD brain tissue |
Neurobiology of disease |
Medium |
11592857
|
| 2001 |
VILIP-1 (VSNL1) increases cGMP levels in transfected C6 and PC12 cells; membrane-associated (myristoylated) VILIP-1 preferentially stimulates particulate guanylyl cyclase (GC), while cytosolic (non-myristoylated) VILIP-1 enhances soluble GC; VILIP-1 physically interacts with the catalytic domain of particulate GC-A and GC-B and with native GC enriched from rat brain, demonstrated by GST pull-down and surface plasmon resonance; VILIP-1 introduced into cerebellar granule cells specifically influences GC-B but not GC-A signaling. |
Transfection in C6/PC12 cells, cGMP assay, GST pull-down, surface plasmon resonance, trituration of recombinant protein into cerebellar granule cells |
Journal of neurochemistry |
High |
11579136
|
| 2002 |
VILIP-1 (VSNL1) undergoes a reversible, stimulus-dependent calcium-myristoyl switch in living hippocampal neurons: GFP-tagged VILIP-1 translocates from diffuse cytosolic distribution to plasma membrane and Golgi membranes upon Ca2+ ionophore treatment or depolarization/glutamate receptor activation; this translocation is fully reversed by EGTA; myristoylation-deficient VILIP-1-GFP does not translocate. |
Live fluorescence microscopy of GFP-tagged VILIP-1 in transfected NG108-15, COS-7 cells and primary hippocampal neurons; Ca2+ ionophore and EGTA manipulation; myristoylation-deficient mutant |
The Journal of neuroscience |
High |
12196554
|
| 2002 |
VILIP-1 and VILIP-3 show distinct Ca2+-dependent subcellular localizations and activate different cellular signaling pathways; VILIP-3 (mainly in Purkinje cells) and VILIP-1 (in granule cells) have different protein interaction partners and different degrees of Ca2+-dependent membrane association, indicating cell-type-specific signaling functions. |
Subcellular fractionation, cGMP signaling assays, protein interaction assays in transfected cells, immunolocalization |
Biochimica et biophysica acta |
Medium |
12445467
|
| 2003 |
VILIP-3-GFP and VILIP-1-GFP both undergo fast and reversible calcium-myristoyl switches in living cell lines and hippocampal neurons, but differ in calcium-dependent translocation to Golgi membranes and in dendritic localization, demonstrating that co-expressed VILIPs can produce highly selective responses to calcium stimuli. |
Live fluorescence microscopy of GFP-tagged proteins in transfected cells and hippocampal neurons |
Molecular and cellular neurosciences |
Medium |
14664824
|
| 2005 |
VILIP-1 (VSNL1) modulates cGMP signaling of guanylyl cyclase B (GC-B) in hippocampal neurons by regulating clathrin-dependent receptor recycling; VILIP-1 and GC-B co-localize in soma and dendrites in hippocampal neurons, and VILIP-1 influences natriuretic peptide-stimulated cGMP levels through effects on membrane trafficking rather than direct catalytic activation. |
Transfection in C6 cells, primary hippocampal neurons, cGMP assay, co-localization immunofluorescence, clathrin-dependent trafficking assay |
Journal of cell science |
Medium |
15923662
|
| 2008 |
VILIP-1 (VSNL1) interacts with the cytoplasmic loop of the α4-subunit of α4β2 nicotinic acetylcholine receptor (nAChR); overexpression of VILIP-1 enhances ACh responsiveness and α4β2 nAChR currents in hippocampal neurons while siRNA knockdown reduces them; the mechanism involves enhanced constitutive exocytosis of α4β2 nAChRs via co-localization with syntaxin-6 (a Golgi-SNARE) in a Ca2+-dependent manner. |
Co-immunoprecipitation, siRNA knockdown, overexpression in hippocampal neurons, electrophysiology (ACh currents), co-localization immunofluorescence with syntaxin-6 |
Molecular and cellular neurosciences |
High |
19063970
|
| 2008 |
Nicotine stimulation triggers a Ca2+-dependent and reversible membrane-translocation (calcium-myristoyl switch) of VILIP-1 in hippocampal interneurons; only α7- but not α4-containing nAChRs elicit this Ca2+-dependent translocation, as shown by selective antagonists dihydro-β-erythroidine (α4 antagonist) and methylallylaconitine (α7 antagonist). |
Live fluorescence microscopy of GFP-VILIP-1 in primary hippocampal neurons, pharmacological receptor antagonists |
Cellular and molecular neurobiology |
Medium |
18925431
|
| 2010 |
VILIP-1 (VSNL1) reduces migration of aggressive squamous cell carcinoma (SCC) cells in a cAMP-dependent manner; VILIP-1 enhances protein expression and membrane localization of adenylyl cyclases (ACs), thereby increasing cAMP levels; cAMP-effectors PKA and EPAC act downstream; cGMP signaling (via NPR-A/B) does not mediate VILIP-1's effect on SCC migration. |
Overexpression in SCC cells, migration assay (transwell), cAMP/cGMP measurement, adenylyl cyclase inhibitor 2',3'-dideoxyadenosine, PKA inhibitor KT5720, EPAC antagonist, mRNA expression profiling |
Molecular carcinogenesis |
Medium |
21480386
|
| 2010 |
Structural analysis revealed that unmyristoylated VILIP-1 binds two Ca2+ sequentially at EF2 and EF3 with affinities K(EF3)=0.1 μM and K(EF2)=1-4 μM; myristoylated VILIP-1 binds Ca2+ with lower affinity (Kd=1.2 μM) and positive cooperativity; NMR demonstrates Ca2+-free VILIP-1 sequesters its myristoyl group (like recoverin) and Ca2+ causes extrusion of the myristate; VILIP-1 forms a Ca2+-independent dimer via residues in EF4 and the EF3-EF4 loop, confirmed by mutagenesis. |
NMR spectroscopy, isothermal titration calorimetry, size exclusion chromatography, site-directed mutagenesis |
The Journal of biological chemistry |
High |
21169352
|
| 2011 |
VILIP-1 (VSNL1) siRNA knockdown in rat hippocampal neurons decreases cAMP levels and reduces dendrite branching; conversely, VILIP-1 overexpression increases cAMP levels and dendrite branching; this effect on neurite branching is attenuated by adenylyl cyclase inhibitor 2',5'-dideoxyadenosine and PKA inhibitor KT5720, placing VILIP-1 upstream of cAMP/PKA in regulating neuronal morphology. |
siRNA knockdown and overexpression in rat hippocampal neurons and SH-SY5Y cells, dendrite morphology analysis, cAMP measurement, pharmacological inhibition of AC and PKA |
Translational psychiatry |
Medium |
22832524
|
| 2011 |
Vsnl1 (mouse VSNL1 ortholog) marks ureteric bud tips in embryonic kidney as a GDNF-regulated target gene; Vsnl1 expression requires GDNF signaling and is absent in Gdnf-null kidneys; Vsnl1 shows mutually exclusive expression with β-catenin transcriptional activation; in mouse collecting duct cell line, Vsnl1 overexpression compromises β-catenin stability, suggesting Vsnl1 counteracts β-catenin signaling. |
Microarray screening, tissue culture of Gdnf-deficient kidneys with exogenous growth factors, immunostaining, overexpression in collecting duct cell lines, β-catenin stability assay |
Journal of the American Society of Nephrology |
Medium |
21289216
|
| 2012 |
VILIP-1 (VSNL1) suppresses EGF-induced epithelial-mesenchymal transition (EMT) in squamous cell carcinoma cells via a cAMP-dependent mechanism: VILIP-1-positive SCCs have high cAMP and low invasiveness; VILIP-1 expression reduces Snail1 transcriptional repressor levels; adenylyl cyclase inhibitor 2',3'-dideoxyadenosine attenuates VILIP-1's suppression of Snail1; elevated cAMP also suppresses EGF-induced migration. |
Overexpression in VILIP-1-negative SCC cells, Snail1 immunoblot, migration assay, adenylyl cyclase inhibitor treatment, EGF stimulation |
PloS one |
Medium |
22479362
|
| 2013 |
VILIP-1 (VSNL1) upregulates functional P2X3 receptors in dorsal root ganglion (DRG) neurons, contributing to bone cancer pain; the interaction between the amino-terminus of VILIP-1 and the carboxyl-terminus of P2X3 receptor is critical for P2X3 surface expression and functional enhancement; VILIP-1 overexpression increases P2X3 expression and neuronal excitability in naive rat DRG neurons; VILIP-1 knockdown inhibits bone cancer pain development by downregulating P2X3 receptors. |
Co-immunoprecipitation, VILIP-1 overexpression and siRNA knockdown in rat DRG neurons, P2X3 surface expression assay, electrophysiology, bone cancer pain behavioral model |
Pain |
High |
23707265
|
| 2022 |
VSNL1 physically interacts with COL10A1 as demonstrated by co-immunoprecipitation; VSNL1 promotes proliferation, migration, and invasion of colorectal cancer cells; COL10A1 upregulation reverses the inhibitory effects of VSNL1 knockdown on these cellular processes. |
Co-IP, siRNA knockdown, CCK8 assay, EdU assay, transwell migration/invasion assay, Western blot |
Annals of clinical and laboratory science |
Medium |
35181619
|
| 2025 |
VSNL1 promotes protection against myocardial ischemia/reperfusion injury through the VILIP-1/GRK2/GLUT4 signaling axis: GPR81 activation increases VILIP-1 expression, reduces GRK2 expression, and increases GLUT4 membrane expression, enhancing glucose uptake in cardiomyocytes; these effects are reversed by GPR81 antagonism or GRK2 inhibition. |
In vivo mouse I/R model, in vitro OGD/R in HL-1 cardiomyocytes, pharmacological GPR81 activation/inhibition, GRK2 inhibitor, GLUT4 membrane fractionation, bulk RNA sequencing |
International journal of biological macromolecules |
Low |
41192713
|
| 2025 |
VSNL1 overexpression in AC16 cardiomyocytes attenuates hypoxia/H2O2-induced DNA damage and apoptosis by activating the CNP/NPR-B signaling pathway; VSNL1 overexpression increases CNP and NPR-B membrane levels and decreases intracellular Ca2+; co-immunoprecipitation shows no direct protein interaction between VSNL1 and CNP, indicating indirect regulation of this pathway. |
Lentiviral overexpression and siRNA knockdown in AC16 cells, western blot, immunofluorescence, γ-H2AX assay, co-immunoprecipitation, qPCR, Ca2+ measurement |
Molecular biotechnology / Molecular medicine reports |
Low |
39924636 41930460
|