| 2006 |
PACSIN1/syndapin1 directly and selectively binds the carboxy-terminal domain of the NMDAR subunit NR3A through its NPF motifs, assembles a complex including dynamin and clathrin, and mediates activity-dependent endocytosis of NR3A-containing NMDARs from the dendritic plasma membrane; disruption of PACSIN1 function causes NR3A accumulation at synaptic sites. |
Co-immunoprecipitation, pulldown assays, dominant-negative disruption in cultured rat hippocampal neurons, live-cell imaging of endocytosis |
Nature neuroscience |
High |
16617342
|
| 2017 |
PACSIN1 is the most abundant interactor of the K+-Cl- cotransporter KCC2 in the mouse brain; shRNA knockdown of PACSIN1 in hippocampal neurons increases KCC2 expression and hyperpolarizes the reversal potential for Cl-, establishing PACSIN1 as a negative regulator of KCC2 and thus of synaptic inhibition. |
Functional proteomics (native KCC2 interactome by mass spectrometry), biochemical validation of PACSIN1-KCC2 interaction, shRNA knockdown with electrophysiological readout |
eLife |
High |
29028184
|
| 2016 |
PACSIN1 plays dual roles in controlling NMDAR-dependent GluA2 (AMPAR subunit) internalization and recycling; the F-BAR and SH3 domains are required for NMDAR-dependent GluA2 internalization, while the variable region (which binds PICK1) is required for correct AMPAR recycling but not internalization. |
pHluorin-GluA2 live-cell imaging, structure-function analysis with domain deletion mutants, NMDAR activation assays in neurons |
Scientific reports |
High |
27488904
|
| 2012 |
PACSIN1 regulates TLR7/9-mediated type I interferon production in plasmacytoid dendritic cells (pDCs); shRNA knockdown in human pDC line inhibits type I IFN response to TLR9 ligand, and PACSIN1-deficient mice show reduced IFN-α production in response to CpG-ODN and virus without affecting proinflammatory cytokine production, indicating a specific role in the type I IFN signaling cascade. |
shRNA knockdown in human pDC cell line, PACSIN1 knockout mice, cytokine measurement by ELISA |
European journal of immunology |
Medium |
22488361
|
| 2018 |
The SH3 domains of PACSIN1, 2, and 3 bind the proline-rich region (PRR) of the TRPV4 N-terminus as a class I polyproline II helix (with a conserved cis-proline break); PACSIN/Syndapin SH3 domain binding rigidifies both the PRR and the adjacent PIP2 binding site, and PACSIN binding influences the PIP2 binding site but not vice versa, establishing a hierarchical interaction network. |
NMR structure determination of PACSIN3 SH3 domain–TRPV4 PRR complex, binding affinity measurements for PACSIN1/2/3 SH3 domains, NMR chemical shift mapping |
Structure |
High |
30244966
|
| 2012 |
PACSIN1 interacts with Tau in axons; PACSIN1 blockade impairs axonal elongation and increases primary axonal branching in mouse DRG neurons by increasing Tau binding to microtubules, causing Tau accumulation in the central domain of growth cones and promoting microtubule network stability. |
Co-immunoprecipitation, dominant-negative PACSIN1 blockade in mouse DRG neurons, microtubule binding assays, immunofluorescence |
The Journal of biological chemistry |
Medium |
23035120
|
| 2021 |
Phosphorylation of Tau at serine residues 396/404 (pTau) decreases Tau:PACSIN1 binding and evokes PACSIN1-dependent functional and structural synapse weakening; knockdown of PACSIN1 increases AMPAR-mediated current at extrasynaptic regions, supporting a role for these proteins in AMPAR trafficking regulation. |
In vitro genetic knock-in of phosphorylation mutant human tau in rat CA1 hippocampal neurons, electrophysiology, Co-immunoprecipitation, shRNA knockdown |
The Journal of neuroscience |
Medium |
34290082
|
| 2022 |
PACSIN1 is required for amphisome-lysosome fusion during basal (nutrient-rich) autophagy but not starvation-induced autophagy; PACSIN1 interacts with the autophagic SNARE protein SNAP29 and is required for proper assembly of STX17 and YKT6 SNARE complexes. PACSIN1 is also required for lysophagy and aggrephagy but not mitophagy, indicating cargo-specific fusion mechanisms. |
PACSIN1 deletion, electron microscopy, co-localization analysis, Co-immunoprecipitation with SNAP29/STX17/YKT6, C. elegans sdpn-1 deletion as ortholog validation |
PLoS genetics |
High |
35771772
|
| 2023 |
PACSIN1 forms a trimolecular complex with TRAF4 and TRAF6 to regulate type I IFN signaling; the disease-associated Q59K mutation augments PACSIN1 binding to N-WASP while decreasing binding to TRAF4, leading to unrestrained TRAF6-mediated type I IFN activation and selective enhancement of TLR7 (but not TLR9) signaling. |
CRISPR/Cas9 introduction of Q59K and null variants, co-immunoprecipitation, luciferase reporter assays, RNA interference, immunofluorescence, flow cytometry |
Arthritis & rheumatology |
High |
36622335
|
| 2019 |
Molecular dynamics simulations show that PACSIN1 F-BAR domain has internal structural flexibility and that two PACSIN1 dimers spontaneously assemble via lateral interactions; the assembled dimers bend tensionless lipid membranes, and a single PACSIN1 dimer senses membrane curvature by preferentially binding buckled membranes at a preferred curvature. |
All-atom and coarse-grained molecular dynamics simulations of PACSIN1 on lipid membranes |
Scientific reports |
Low |
31601944
|
| 2024 |
PACSIN1 released from injured axons binds to the Schwann cell receptor LRP1; recombinant PACSIN1 activates c-Jun and ERK1/2 in Schwann cells in an LRP1-dependent and NMDA-R-dependent manner, and transactivates the receptor tyrosine kinase TrkC to promote Schwann cell repair signaling, migration, and survival. |
LRP1-Fc ligand capture from injured nerve, Co-IP validation, recombinant PACSIN1 treatment with LRP1 silencing and TrkC inhibition/silencing, intraneural injection in conditional Lrp1-knockout mice, transcriptome profiling |
Glia |
High |
38372375
|
| 2024 |
PACSIN1 promotes lysosomal fusion and selective autophagy of MHC-I, thereby degrading MHC-I and suppressing antigen presentation and CD8+ T-cell infiltration in gastric cancer; PACSIN1 deficiency inhibits MHC-I autophagy and increases MHC-I surface expression. |
PACSIN1 knockout, FISH colocalization of PACSIN1 and MHC-I, flow cytometry for MHC-I and CD8+ T cells, in vivo tumor models |
Acta biochimica et biophysica Sinica |
Medium |
38826133
|
| 2025 |
UBE3A (the Angelman syndrome E3 ubiquitin ligase) polyubiquitinates PACSIN1 with K48-linked chains to target it for proteasomal degradation; loss of UBE3A increases PACSIN1 protein abundance in human cortical neurons, with implications for AMPA receptor recycling. |
LC-MS/MS proteomics of UBE3A knockout vs. wild-type human iPSC-derived cortical neurons, ubiquitination assay |
Molecular and cellular biology |
Medium |
40671377
|
| 2020 |
NMR backbone and side-chain assignments of the human PACSIN1 SH3 domain identified five β-strands linked by flexible loops, consistent with a canonical SH3 fold, providing structural context for its interaction network. |
Solution NMR (2D HSQC/HMQC and multiple 3D experiments), homology modeling |
Biomolecular NMR assignments |
Medium |
32236802
|