| 1999 |
Snapin directly binds SNAP-25 and associates with the SNARE complex; it is enriched in neurons and localized on synaptic vesicle membranes. The C-terminal fragment of Snapin blocks the association of the SNARE complex with synaptotagmin, and introduction of Snapin-CT into presynaptic neurons reversibly inhibited synaptic transmission. |
Yeast two-hybrid, pulldown, co-immunoprecipitation, peptide microinjection into SCG neurons, electrophysiology |
Nature neuroscience |
High |
10195194
|
| 2001 |
PKA phosphorylates Snapin at serine 50. Phosphorylation (or S50D phosphomimetic mutation) significantly increases Snapin binding to SNAP-25 and enhances association of synaptotagmin with the SNARE complex. In adrenal chromaffin cells, S50D overexpression increases the number of release-competent vesicles. In vivo, cAMP analogue treatment of hippocampal slices induces Snapin phosphorylation and enhances both Snapin–SNAP-25 and synaptotagmin–SNARE interactions. |
Site-directed mutagenesis (S50D, S50A), in vitro kinase assay, co-immunoprecipitation, patch-clamp capacitance measurements in chromaffin cells, rat hippocampal slice experiments |
Nature cell biology |
High |
11283605
|
| 2003 |
Snapin is expressed ubiquitously (not brain-specific) and interacts with SNAP-23, the widely expressed SNAP-25 homologue; the C-terminal helical domain of Snapin contains the SNAP-23-binding site. Snapin can form a ternary complex with SNAP-23 and syntaxin-4, indicating a role in non-neuronal SNARE complexes. Subcellular fractionation shows Snapin exists in both cytosolic and peripheral membrane-bound pools in adipocytes. |
Protein–protein interaction assays (pulldown, co-immunoprecipitation), subcellular fractionation, GFP fusion overexpression, ternary complex reconstitution |
The Biochemical journal |
Medium |
12877659
|
| 2004 |
Snapin is a subunit of BLOC-1 (biogenesis of lysosome-related organelles complex-1). Snapin co-immunoprecipitates and co-fractionates with all known BLOC-1 subunits (Pallidin, Muted, Cappuccino, Dysbindin). In pallid mouse cells, steady-state Snapin levels are significantly reduced secondary to Pallidin mutation, consistent with assembly-dependent stability. Yeast two-hybrid analysis reveals a network of binary interactions among BLOC-1 subunits. |
Co-immunoprecipitation, size-exclusion chromatography, immunoblotting in pallid mouse cells, yeast two-hybrid |
The Journal of biological chemistry |
High |
15102850
|
| 2004 |
Snapin interacts with the N-terminus (residues 1–86) of type VI adenylyl cyclase (ACVI), with the interaction domain on Snapin mapped to residues 33–51. Snapin expression specifically eliminates PKC-mediated suppression of ACVI activity without affecting PKA- or calcium-mediated regulation. This effect requires direct interaction: a Snapin(Δ33–51) mutant that cannot bind ACVI fails to reverse PKC inhibition. |
Yeast two-hybrid (bait: ACVI N-terminus), co-immunoprecipitation, mutational analysis, adenylyl cyclase activity assay, co-localization in hippocampal neurons |
The Journal of biological chemistry |
Medium |
15319443
|
| 2004 |
PKA-dependent phosphorylation of Snapin (S50D mimetic) in hippocampal neurons decreases readily releasable vesicle pool size, increases release probability of individual vesicles, and increases depression rate during high-frequency stimulation. The non-phosphorylatable S50A mutant does not alter pool size or release probability. Dialysis of Sp-cAMPS also leads to increased synaptic depression in cells overexpressing wild-type Snapin. |
Overexpression of S50D/S50A mutants in hippocampal neurons, whole-cell patch-clamp electrophysiology, Sp-cAMPS dialysis |
The Journal of neuroscience |
High |
15269257
|
| 2005 |
Snapin knock-out mice show impaired association of synaptotagmin-1 with SNAP-25 in brain homogenates. In embryonic chromaffin cells, absence of Snapin significantly reduces calcium-dependent exocytosis by decreasing the number of vesicles in releasable pools. Snapin is enriched in purified large dense-core vesicles and associates with synaptotagmin-1. Overexpression of Snapin fully rescues the exocytosis defect in mutant cells. |
Snapin knock-out mice, co-immunoprecipitation, patch-clamp capacitance measurements, LDV purification, rescue by Snapin re-expression |
The Journal of neuroscience |
High |
16280592
|
| 2005 |
Snapin binds cypin via its C-terminal coiled-coil domain (H2); this interaction requires cypin's CRMP homology domain (the same site where tubulin binds). Snapin competes with tubulin for binding to cypin, resulting in decreased microtubule assembly. Overexpression of Snapin in hippocampal neurons decreases primary dendrite number and increases branching probability, indicating Snapin regulates dendrite patterning by modulating cypin-promoted microtubule assembly. |
Yeast two-hybrid, affinity chromatography, co-immunoprecipitation, in vitro microtubule assembly assay, overexpression in primary hippocampal neurons, morphometric analysis |
Molecular biology of the cell |
Medium |
16120643
|
| 2005 |
EBAG9 interacts with Snapin (yeast two-hybrid confirmed). EBAG9–Snapin interaction inhibits regulated secretion of neuropeptide Y from PC12 cells. Mechanistically, EBAG9 decreases phosphorylation of Snapin, which in turn reduces Snapin's association with SNAP-25 and SNAP-23. |
Yeast two-hybrid, co-immunoprecipitation, neuropeptide Y secretion assay in PC12 cells, phosphorylation analysis |
Molecular biology of the cell |
Medium |
15635093
|
| 2006 |
Dysbindin-1 binds Snapin in vitro and in mouse/human brain; both proteins are concentrated in synaptic vesicle membrane fractions. Immunoelectron microscopy localises dysbindin-1 to synaptic vesicles of glutamatergic axospinous terminals and to postsynaptic densities and microtubules. A 30-residue peptide in dysbindin (residues 90–119) mediates interaction with Snapin, and Snapin is destabilised in dysbindin-null (sandy) mice. |
Co-immunoprecipitation, tissue fractionation, immunoelectron microscopy, peptide mapping, immunoblotting in sdy mice |
Human molecular genetics |
High |
16980328 18774265
|
| 2006 |
Snapin interacts with ryanodine receptor 2 (RyR2) via a 170-residue cytosolic loop (RyR2 residues 4596–4765); this interaction is conserved across RyR1, RyR2, and RyR3. The Snapin–RyR1 association sensitises the channel to Ca2+ activation in ryanodine-binding studies. The ryanodine receptor and SNAP-25 share an overlapping binding site on Snapin's C-terminus. |
Pulldown with peptide fragments, co-immunoprecipitation with native RyR, [3H]ryanodine binding assay, deletion analysis, competition experiment |
Journal of cell science |
Medium |
16723744
|
| 2006 |
CK1δ interacts with Snapin (yeast two-hybrid, co-immunoprecipitation) and phosphorylates Snapin in vitro. Both proteins co-localise in the perinuclear region, where Snapin associates with Golgi apparatus membranes. |
Yeast two-hybrid, co-immunoprecipitation, in vitro kinase assay, co-localization by immunofluorescence |
FEBS letters |
Medium |
17101137
|
| 2007 |
Snapin interacts with Exo70 subunit of the exocyst via an N-terminal coiled-coil domain in Exo70 and the C-terminal helical region of Snapin. Exo70 competes with SNAP-23 for Snapin binding. RNAi-mediated depletion of Snapin in adipocytes inhibits insulin-stimulated glucose uptake, implicating Snapin in GLUT4 trafficking. |
Co-immunoprecipitation, pulldown assays, domain mapping, Snapin siRNA knockdown in adipocytes, glucose uptake assay |
The Journal of biological chemistry |
Medium |
17947242
|
| 2007 |
Snapin interacts with the C-terminus of alpha1A-adrenoceptor (α1A-AR) and co-immunoprecipitates with TRPC6 and α1A-AR. Snapin co-transfection augments α1A-AR-stimulated sustained Ca2+ influx via receptor-operated channels; disrupting the Snapin-binding domain or Snapin siRNA knockdown attenuates this effect. α1A-AR activation increases Snapin–TRPC6 interaction and recruits TRPC6 to the cell surface. |
Yeast two-hybrid (identified interaction), co-immunoprecipitation, siRNA knockdown, intracellular Ca2+ measurements, cell-surface TRPC6 assay in PC12 cells |
The Journal of biological chemistry |
Medium |
17684020
|
| 2007 |
Snapin interacts with the UT-A1 urea transporter intracellular loop (residues 409–594); the C-terminal coiled-coil domain (H2) of Snapin is required. Co-injection of Snapin with UT-A1 cRNA in Xenopus oocytes significantly increases urea influx; in the absence of Snapin, UT-A1 combined with t-SNARE components syntaxin-4 and SNAP-23 shows decreased urea influx. |
Yeast two-hybrid, GST pulldown, co-immunoprecipitation, Xenopus oocyte urea transport assay, confocal co-localization |
The Journal of biological chemistry |
Medium |
17702749
|
| 2008 |
Loss of dysbindin in sandy (sdy) mice reduces steady-state Snapin protein levels; a 30-residue dysbindin peptide (residues 90–119) mediates interaction with Snapin, indicating dysbindin stabilises Snapin in vivo. |
Immunoblotting in sdy mice, peptide mapping of interaction domain |
Schizophrenia research |
Medium |
18774265
|
| 2009 |
Snapin deficiency in cortical neurons results in EPSCs with multiple peaks and increased rise/decay times (desynchronized SV fusion), reduced mini-EPSC frequency, and smaller readily releasable pool. Transient Snapin expression rescues kinetics defects. A dimerization-defective Snapin-C66A mutant with impaired SNAP-25 and synaptotagmin interactions reduces RRP size but has less effect on synchrony, suggesting a dual role: Snapin dimerization fine-tunes synchronous fusion while monomer interactions regulate priming. |
Snapin-deficient mouse neurons, whole-cell patch-clamp, overexpression rescue, C66A dimerization mutant |
Neuron |
High |
19217378
|
| 2009 |
Snapin associates with late endocytic compartments and interacts with late endosome-targeted SNARE complex components syntaxin 8 and Vti1b. Deleting snapin in mice leads to selective accumulation of LAMP-1, syntaxin 8, and Vti1b in late endocytic organelles, indicating Snapin regulates the late endocytic fusion machinery. |
Co-immunoprecipitation, subcellular fractionation, immunofluorescence, snapin KO mouse model, immunoblotting |
Bioscience reports |
Medium |
19335339
|
| 2010 |
Snapin acts as a dynein motor adaptor that recruits dynein to late endosomes for retrograde transport; Snapin deficiency impairs late endosomal-lysosomal trafficking, leads to clustering of late endosomes in neuronal processes, and impairs autophagy-lysosomal function and autolysosome clearance, reducing neuron viability. Reintroducing the snapin transgene rescues these defects. |
Snapin KO mice, live imaging, co-immunoprecipitation (Snapin–dynein), retrograde transport assays, autolysosome accumulation assay, genetic rescue |
Neuron (referenced via PMID:20920785 review and PMID:21233602) |
High |
20920785 21233602
|
| 2011 |
Snapin mediates GLP-1/incretin action on insulin secretion: PKA-dependent phosphorylation of Snapin increases interaction among insulin secretory vesicle-associated proteins, potentiating glucose-stimulated insulin secretion (GSIS). In diabetic islets with impaired GSIS, Snapin phosphorylation is reduced; expression of a phosphomimetic Snapin mutant restores GSIS. |
PKA phosphorylation assay, co-immunoprecipitation in islets, Snapin phosphomimetic expression in diabetic islets, insulin secretion assay |
Cell metabolism |
Medium |
21356520
|
| 2011 |
AC6 forms a complex with Snapin and SNAP-25 in a phosphorylation-dependent manner at its N-terminus (AC6-N). This complex suppresses neurite outgrowth. Disruption by Snapin(Δ33–51) or Snapin(S50A) mutants (which cannot bind AC6 or SNAP-25 respectively) reverses the inhibitory effect of AC6 on neurite extension. Overexpression of SNAP-25 also reverses AC6 action, indicating SNAP-25 competes in the complex. |
Pull-down, co-immunoprecipitation, AC activity assay, neurite length quantification in hippocampal neurons and Neuro2A, AC6 KO neurons, Snapin knockdown |
Molecular and cellular biology |
Medium |
21986494
|
| 2012 |
Snapin, as a dynein adaptor, mediates retrograde axonal transport of TrkB (BDNF) signaling endosomes. Deleting snapin or disrupting Snapin–dynein interaction abolishes TrkB retrograde transport, impairs BDNF-induced retrograde signaling from axonal terminals to the nucleus, and decreases dendritic growth of cortical neurons. Re-introducing the snapin gene rescues all defects. |
Snapin KO mice, compartmentalized microfluidic cultures of cortical neurons, live imaging of fluorescently tagged TrkB endosomes, Snapin–dynein interaction-disrupting mutants, nuclear signaling assay, dendritic morphometry, genetic rescue |
Cell reports |
High |
22840395
|
| 2012 |
Atg14L directly binds Snapin and co-localizes with it. This interaction facilitates endosome maturation without affecting autophagic cargo degradation. Atg14L knockdown delays late-stage endocytic trafficking (retarded receptor degradation); this is rescued by wild-type Atg14L or a Beclin-1-binding mutant but not by a Snapin-binding mutant of Atg14L. |
Co-immunoprecipitation, co-localization, siRNA knockdown, receptor degradation kinetics assay, rescue with Atg14L point mutants |
Journal of cell science |
Medium |
22797916
|
| 2012 |
Snapin is required for presynaptic homeostatic plasticity at the Drosophila NMJ. Loss of snapin blocks homeostatic modulation of presynaptic vesicle release following both pharmacological and genetic inhibition of postsynaptic glutamate receptors. Snapin does not alter baseline transmission, synapse morphology, or active zone number. Genetic evidence indicates snapin functions with dysbindin to modulate vesicle release, and interaction of Snapin with SNAP-25 is also required for synaptic homeostasis. |
Drosophila snapin loss-of-function, electrophysiology at NMJ, pharmacological GluR inhibition, double mutant (snapin;dysbindin) genetic epistasis |
The Journal of neuroscience |
High |
22723711
|
| 2012 |
The phosphomimetic mutation S50D and the Cys-66 dimerization mutation alter Snapin protein structure and stability in vitro: S50D loses α-helical structure and thermal stability and disrupts tetrameric assemblies to favour dimers, while C66A abolishes subunit dimerization but not higher-order oligomers. S50D exhibits the strongest binding to the SNARE complex in vitro, consistent with enhanced cellular activity of PKA-phosphorylated Snapin. |
CD spectroscopy, fluorescence anisotropy, thermal stability assay, size-exclusion chromatography, in vitro SNARE pulldown with recombinant proteins |
Biochemistry |
Medium |
22471585
|
| 2013 |
LRRK2 interacts with Snapin via its ROC and N-terminal domains and phosphorylates Snapin at threonine 117 in vitro. The phosphomimetic T117D mutant decreases Snapin–SNAP-25 interaction and, when added to rat brain lysate, reduces synaptotagmin association with the SNARE complex. LRRK2-dependent phosphorylation of Snapin in hippocampal neurons decreases the number of readily releasable vesicles and extent of exocytotic release. |
Yeast two-hybrid, GST pulldown, in vitro kinase assay, mutagenesis (T117D), co-immunoprecipitation, electrophysiology in hippocampal neurons |
Experimental & molecular medicine |
Medium |
23949442
|
| 2013 |
Snapin, as a dynein adaptor for late endosomes, mediates BACE1 retrograde transport to lysosomes for degradation. In hAPP mutant neurons, reduced Snapin–dynein coupling leads to BACE1 accumulation in late endocytic organelles and impaired lysosomal targeting, enhancing APP processing. Overexpressing Snapin in hAPP neurons reduces β-site cleavage of APP by enhancing BACE1 turnover. |
Snapin KO mice, live axonal transport imaging, snapin–dynein interaction-disrupting mutants, BACE1 trafficking and degradation assays, APP processing/Aβ measurement, genetic rescue |
Cell reports |
High |
24373968
|
| 2013 |
In C. elegans, loss of snpn-1 (Snapin) reduces the number of docked, fusion-competent synaptic vesicles but does not affect kinetics of transmission. Double mutant analysis of snt-1;snpn-1 indicates SNPN-1's role in vesicle docking/priming is independent of synaptotagmin, suggesting Snapin stabilises SNARE complex formation upstream of synaptotagmin's Ca2+-sensing function. |
C. elegans snpn-1 loss-of-function, electrophysiology at NMJ, electron microscopy (docked vesicle count), snt-1;snpn-1 double mutant epistasis |
PloS one |
Medium |
23469084
|
| 2015 |
Snapin acts as a dynein adaptor for retrograde transport of late endosomes (LEs), and interacts with dysbindin (BLOC-1 subunit). Expressing dynein-binding-defective Snapin mutants induces SV accumulation at presynaptic terminals. Overexpressing Snapin reduces SV pool size by enhancing SV trafficking to the endolysosomal pathway. Snapin–dysbindin interaction regulates SV positional priming through BLOC-1/AP-3-dependent sorting; LE retrograde transport regulates SV pool size, while BLOC-1/AP-3 sorting fine-tunes Ca2+-sensitivity of SV release. |
Snapin KO neurons, dynein-binding mutants, SV-targeted Ca2+ sensor, overexpression, live imaging, electrophysiology |
The EMBO journal |
High |
26108535
|
| 2016 |
SNAPIN is required for lysosomal acidification and autophagosome maturation in macrophages. Silencing SNAPIN impairs cathepsin D activation and lysosomal hydrolysis, and causes lysosomal proton leak (the primary mechanism) with a modest reduction in H+ pump activity, leading to incomplete lysosomal hydrolysis and impaired autophagy flux. |
siRNA knockdown in primary human macrophages, ratiometric fluorescence live-cell imaging of lysosomal pH, cathepsin D activity assay, lysosomal fusion assay, autophagy flux measurement |
Autophagy |
Medium |
27929705
|
| 2016 |
Snapin directly interacts with Cav1.3 L-type Ca2+ channel and promotes ubiquitin-proteasomal degradation of Cav1.3, reducing total and membrane Cav1.3 expression and ICa-L density. SNAP-23 competitively reverses Snapin-induced Cav1.3 downregulation. |
Yeast two-hybrid, GST pulldown, co-immunoprecipitation in HEK cells and mouse atrial myocytes, overexpression, patch-clamp, ubiquitination assay, competition with SNAP-23 |
Cellular signalling |
Medium |
27915047
|
| 2016 |
Snapin promotes HIV-1 trans-infection of CD4+ T cells by dampening TLR8 signaling in dendritic cells. Inhibition of Snapin enhances HIV-1 localisation with TLR8+ early endosomes, triggers pro-inflammatory response, and inhibits trans-infection. Snapin acts as a general regulator of endosomal maturation and inhibits TLR8 signaling independently of HIV-1. |
Phosphoproteomic screen, siRNA knockdown in DCs, co-localisation microscopy, TLR8 signaling assay, HIV-1 trans-infection assay |
The EMBO journal |
Medium |
28923824
|
| 2017 |
Snapin directly binds the C-terminal domain of the dopamine transporter (DAT). Snapin co-localises with DAT in dopaminergic neurons in vivo and in vitro. Snapin co-expression produces a significant decrease in DAT uptake activity. Snapin downregulation in mice increases DAT levels and transport activity, thereby increasing DA concentration and locomotor response to amphetamine. |
Two-hybrid screening, co-immunoprecipitation, co-localisation, DAT uptake assay, Snapin KD in vivo (mice), locomotor assay, 3D interaction model |
Neuropsychopharmacology |
Medium |
28905875
|
| 2021 |
p38α-MAPK directly phosphorylates Snapin (identified phosphorylation site: serine 112 by mass spectrometry and site-directed mutagenesis). Deletion of p38α-MAPK in neurons decreases Snapin serine phosphorylation, increases retrograde transport of BACE1 in axons, and reduces BACE1 at synaptic terminals. S112A substitution abolishes the p38α-KD-induced reduction in BACE1 activity, protein level, and lysosomal targeting, confirming S112 as the functional phosphorylation site. |
APP-transgenic mice, p38α neuron-specific KO, in vitro kinase assay, mass spectrometry, site-directed mutagenesis (S112A), BACE1 retrograde transport imaging, BACE1 activity assay in SH-SY5Y cells |
FASEB journal |
Medium |
34118085
|
| 2022 |
DYRK3 directly phosphorylates Snapin at threonine 14. Phosphorylation at T14 increases Snapin interactions with dynein and synaptotagmin-1. Phospho-T14 Snapin positively modulates mitochondrial retrograde transport in cortical neurons and increases the recycling pool size of synaptic vesicles, contributing to neuronal viability. |
Yeast two-hybrid, in vitro kinase assay, phosphosite mutagenesis (T14), co-immunoprecipitation, live mitochondrial transport imaging in cortical neurons, electrophysiology (recycling pool size) |
Cell death discovery |
Medium |
36585413
|
| 2025 |
CK1δ-mediated hyperphosphorylation of Snapin (induced by HIV-1 Vpr) disrupts lysosomal positioning and motility in neurons. Selective CK1δ inhibition restores lysosomal acidification, positioning, and mitophagy. This defines a Vpr–CK1δ–Snapin axis driving lysosomal dysfunction in neurons. |
Vpr treatment of neurons, CK1δ inhibitor, lysosomal positioning/motility assay, lysosomal acidification assay, mitophagy assay; co-IP confirmation of CK1δ–Snapin interaction |
iScience |
Medium |
41567242
|
| 2025 |
Snapin binds CBS (cystathionine β-synthase; confirmed by molecular docking and co-immunoprecipitation), disrupting H2S metabolic homeostasis and reducing endogenous H2S levels after mTBI. Reduced H2S limits S-sulfhydration of pro-CTSD, promoting its maturation into active CTSD and inducing PANoptosis. Conditional neuronal knockdown of Snapin attenuates neurodegeneration and improves functional recovery in mice. |
CCI mTBI mouse model, AAV-shSnapin conditional KD, co-immunoprecipitation (Snapin–CBS), molecular docking, modified biotin switch assay (CTSD S-sulfhydration), sulfide electrode H2S measurement, PANoptosis protein analysis, behavioral testing |
Journal of advanced research |
Medium |
41558604
|
| 2025 |
SNAPIN facilitates degradation of KEAP1 via the autophagolysosomal pathway; SNAPIN directly binds KEAP1, promoting its lysosomal turnover, which stabilises NRF2 and upregulates GPX4, thereby reducing lipid peroxidation and inhibiting ferroptosis in hepatocellular carcinoma cells. |
SNAPIN overexpression/knockdown in HCC cells, co-immunoprecipitation (SNAPIN–KEAP1), lysosomal degradation inhibition assay, NRF2/GPX4 immunoblotting, ferroptosis induction assay |
Cancer science |
Low |
41190709
|