Affinage

PICK1

PRKCA-binding protein · UniProt Q9NRD5

Length
415 aa
Mass
46.6 kDa
Annotated
2026-06-10
100 papers in source corpus 53 papers cited in narrative 53 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PICK1 is a dual-domain (PDZ + BAR) scaffold that couples the trafficking of membrane proteins to membrane lipid and actin dynamics, functioning centrally in activity-dependent AMPA receptor trafficking and synaptic plasticity (PMID:18367088, PMID:16543133). Its PDZ domain engages the C-termini of a broad set of membrane partners — PKCα, AMPA receptor GluR2/GluA2 subunits, the dopamine transporter, ASIC channels, mGluR7a and others — using canonical type II, non-canonical type I, and dual internal binding modes that allow ligands such as PKCα and GluR2 to compete for overlapping but distinct subsites (PMID:9405395, PMID:10340301, PMID:15247289, PMID:25023278). By scaffolding activated PKCα onto substrates, PICK1 directs phosphorylation of GluR2 at Ser880 and of ASIC2a, releasing GluR2 from its GRIP/ABP anchors and modulating channel currents (PMID:11466413, PMID:12399460, PMID:16055064). The BAR domain binds phosphoinositide membranes, senses membrane curvature through an N-terminal amphipathic helix, and inhibits Arp2/3-mediated actin polymerization; these activities are kept autoinhibited until membrane recruitment via a PDZ- and linker-dependent mechanism and are required for synaptic targeting, AMPAR clustering, dendritic spine remodeling, and LTD (PMID:16510715, PMID:17914463, PMID:18297063, PMID:18466293, PMID:21252856, PMID:29768204). PICK1 acts as a Ca2+ sensor through an N-terminal acidic motif that, upon Ca2+ binding, retains internalized AMPARs intracellularly to enable NMDAR-dependent LTD, while PICK1–AP2 and PICK1–dynamin interactions drive clathrin-mediated AMPAR endocytosis (PMID:16138078, PMID:21147983, PMID:28855251). Its scaffolding output is tuned by palmitoylation (DHHC8), Ser416 phosphorylation (GSK-3β), monoubiquitination (Parkin), and competing partners including Arf1-GTP and NCS-1 (PMID:24068808, PMID:26472923, PMID:17553932, PMID:23889934, PMID:19109914). Beyond the synapse, PICK1 forms heteromeric BAR complexes with ICA69 and the testis paralog ICA1L to drive biogenesis of dense-core and secretory vesicles from the trans-Golgi network in endocrine cells and to build proacrosomal granules during spermiogenesis, with PICK1 loss causing globozoospermia and impaired hormone storage (PMID:18032668, PMID:23630454, PMID:26306493, PMID:19258705).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 1995 High

    Established PICK1's founding identity as a PKCα-interacting protein and a PKC substrate, defining it as a kinase-adaptor candidate.

    Evidence Yeast two-hybrid against the PKCα catalytic domain with in vitro/in vivo phosphorylation and perinuclear localization

    PMID:7844141

    Open questions at the time
    • Did not define the binding domain or other partners
    • Physiological substrates of the scaffolded kinase unknown at this stage
  2. 1997 High

    Mapped the PKCα interaction to a PDZ domain recognizing a C-terminal motif and showed PICK1 homooligomerizes, framing it as a modular, self-associating scaffold.

    Evidence PDZ carboxylate-binding loop mutagenesis with GST pulldown and yeast two-hybrid, plus C. elegans conservation

    PMID:9405395

    Open questions at the time
    • Oligomerization interface not structurally resolved
    • BAR domain function not yet recognized
  3. 1999 High

    Extended PICK1's PDZ repertoire to AMPA receptor GluR2/3 C-termini and demonstrated receptor clustering, linking PICK1 directly to glutamatergic synapse organization.

    Evidence Co-IP, GST pulldown, immunofluorescence and heterologous clustering assays; PDZ Lys-27 mutagenesis showing GluR2/PKCα competition

    PMID:10027300 PMID:10340301

    Open questions at the time
    • Functional consequence for receptor trafficking not yet established
    • Splice-variant selectivity mechanism incompletely defined
  4. 2001 High

    Showed PICK1 co-targets activated PKCα with GluR2 to spines, enabling Ser880 phosphorylation and reduced surface GluR2 — a mechanism for PKC-facilitated AMPAR removal.

    Evidence Activation-dependent Co-IP, neuronal immunofluorescence, surface biotinylation

    PMID:11466413

    Open questions at the time
    • Did not resolve the endocytic machinery involved
    • Role of BAR domain not addressed
  5. 2000 High

    Broadened the partner set to mGluR7a, DAT, ASICs and active ARF1/3, establishing PICK1 as a general PDZ adaptor that clusters and modulates diverse membrane proteins and their PKC phosphorylation.

    Evidence Yeast two-hybrid, GST pulldown, Co-IP, in vitro kinase assays, clustering and uptake assays across multiple receptors/transporters

    PMID:10623590 PMID:11007882 PMID:11144358 PMID:11343649 PMID:11739374

    Open questions at the time
    • ARF1 interaction rests on yeast two-hybrid only
    • Whether clustering reflects retention versus recruitment was unresolved
  6. 2002 High

    Placed PICK1 in functional ion-channel and receptor pathways and revealed NSF/SNAP-mediated disassembly of GluR2–PICK1 as a switch governing AMPAR synaptic stabilization.

    Evidence In vitro complex assembly/ATPase disassembly, electrophysiology with PDZ-blocking peptides and 32P labeling of ASIC2a

    PMID:11466413 PMID:11931741 PMID:12065412 PMID:12399460

    Open questions at the time
    • How NSF activity is triggered physiologically not defined
    • ASIC2a current potentiation mechanism downstream of phosphorylation incomplete
  7. 2004 High

    Resolved that PICK1's single PDZ domain uses distinct subsites for type I (PKCα) and type II (GluR2) ligands, explaining how one domain coordinates competing partners.

    Evidence K27E differential mutagenesis with pulldown, Co-IP and clustering assays

    PMID:15247289

    Open questions at the time
    • Structural basis of dual specificity not yet visualized
    • In vivo competition dynamics not quantified
  8. 2005 High

    Quantified PDZ ligand affinities and discovered the BAR domain as a phosphoinositide- and Ca2+-sensing module that regulates GluR2 binding and is required for AMPAR endocytosis.

    Evidence Fluorescence polarization, Ca2+-binding and lipid-binding assays, BAR/PDZ intramolecular interaction mapping, neuronal trafficking assays

    PMID:15774468 PMID:15797551 PMID:16055064 PMID:16138078

    Open questions at the time
    • Coupling between Ca2+ sensing and lipid binding not mechanistically unified
    • BAR–ABP/GRIP interplay incompletely defined structurally
  9. 2006 High

    Demonstrated that both PDZ and BAR (lipid-binding) domains are obligatory for synaptic targeting and cerebellar/hippocampal LTD, establishing PICK1 as a two-domain effector of plasticity.

    Evidence Liposome binding with mutagenesis, PICK1 KO with domain-mutant rescue, LTD electrophysiology

    PMID:16510715 PMID:16543133

    Open questions at the time
    • Precise membrane intermediate sculpted by BAR not visualized in neurons
    • Quantitative contribution of each domain to LTD steps unresolved
  10. 2007 High

    Identified post-translational and lipid-direct regulation (Parkin monoubiquitination, PDZ–lipid binding via a CPC motif) and the principal BAR partner ICA69, distinguishing synaptic from non-synaptic PICK1 pools.

    Evidence Ubiquitination assays in Parkin KO neurons, lipid-binding mutagenesis, reciprocal Co-IP and liposome assays for ICA69, PDZ crystal structure

    PMID:17384233 PMID:17553932 PMID:17914463 PMID:18032668 PMID:18549785

    Open questions at the time
    • Functional consequence of monoubiquitination beyond ASIC modulation unclear
    • Crystal structure used self-binding extensions rather than physiological ligands
  11. 2008 High

    Defined PICK1 as a calcium-sensing bidirectional plasticity regulator with autoinhibited BAR activity, an Arp2/3-inhibiting actin function, NCS-1 BAR partner, and an in vivo link to absence epilepsy via mGluR7a.

    Evidence PICK1 KO and PDZ-blocking electrophysiology (LTP/LTD), membrane-recruitment imaging, in vitro Arp2/3 inhibition with RNAi, NCS-1 Co-IP, EEG in peptide/KO models

    PMID:18297063 PMID:18367088 PMID:18466293 PMID:18641645 PMID:19109914

    Open questions at the time
    • How membrane recruitment relieves BAR autoinhibition structurally unresolved
    • Link between actin inhibition and receptor endocytosis steps incompletely ordered
  12. 2009 High

    Connected PICK1 to acrosome biogenesis and provided a pharmacological PDZ inhibitor (FSC231), demonstrating roles beyond synapses and a tool for dissecting PDZ-dependent plasticity.

    Evidence PICK1 KO mouse globozoospermia phenotype with GOPC/CK2α' Co-IP and EM; fluorescence polarization screening and FSC231 validation by Co-IP, recycling assay and electrophysiology

    PMID:19258705 PMID:20018661

    Open questions at the time
    • Mechanism linking Golgi granule sculpting to acrosome formation not fully resolved
    • Off-target effects of FSC231 not exhaustively excluded
  13. 2010 High

    Pinpointed the N-terminal acidic Ca2+-binding motif as the determinant of intracellular retention of internalized AMPARs, separating PICK1's role in retention from initial endocytosis during LTD.

    Evidence shRNA rescue with PICK1 Ca2+-binding mutants, pHluorin AMPAR trafficking, electrophysiology

    PMID:21147983

    Open questions at the time
    • Structural nature of the Ca2+-induced conformational change not solved
    • Compartment of retention not molecularly defined
  14. 2011 High

    Established that PICK1's Arp2/3 inhibition controls dendritic spine size and is required for LTD, and that PICK1 loss occludes homeostatic synaptic scaling, embedding it in multiple plasticity regimes.

    Evidence RNAi/overexpression with Arp2/3-binding mutants, spine imaging, PICK1 KO scaling experiments with biotinylation and electrophysiology

    PMID:21252856 PMID:21307255

    Open questions at the time
    • Quantitative coupling of actin inhibition to membrane curvature generation unresolved
    • Scaling mechanism downstream of altered GluA2 composition incomplete
  15. 2012 High

    Expanded PICK1 into receptor degradation and recycling control, scaffolding TβRI to caveolin-1 for degradation and slowing reinsertion of PDZ partners from Rab11 recycling compartments.

    Evidence Co-IP, ubiquitination and raft fractionation for TβRI; ELISA-based surface trafficking of chimeric receptors with inducible PICK1

    PMID:22303009 PMID:22710801

    Open questions at the time
    • Generalizability of recycling control to native partners not established
    • TβRI degradation mechanism rests on a single lab
  16. 2013 High

    Demonstrated BAR-domain membrane sculpting in secretory vesicle biogenesis and identified additional regulatory inputs (DHHC8 palmitoylation, Arf1-GTP gating of Arp2/3 inhibition, PACSIN partners), unifying PICK1's lipid, actin and endocytic activities.

    Evidence KO mice and in vitro tubulation/EM for vesicle biogenesis; palmitoylation and Arf1-mutant assays with electrophysiology; PACSIN2 KO rescue and Co-IP

    PMID:23630454 PMID:23889934 PMID:23918399 PMID:24068808

    Open questions at the time
    • Hierarchy of these regulatory inputs during a single LTD event not ordered
    • How Arf1 GAP signaling is initiated by NMDAR not fully traced
  17. 2014 High

    Refined the structural logic of PICK1: three PDZ binding modes, BAR-domain control of dense-core vesicle number/size, plus new roles in GluA2 ER export and dendritic Ago2-mediated translation.

    Evidence NMR/mutagenesis of PDZ binding modes; chromaffin-cell KO with amperometry and domain-mutant rescue; Co-IP and surface assays for CaMKII/GluA2 ER export and Ago2 reporter assays

    PMID:24723684 PMID:24831007 PMID:25023278 PMID:25100601

    Open questions at the time
    • Ago2 interaction mechanistically thin (Co-IP/imaging only)
    • ER-export role rests on a single lab with pharmacological dissection
  18. 2015 High

    Resolved the supramolecular architecture (offset parallel BAR–BAR dimers/tetramers with flexible PDZ positioning), defined GSK-3β Ser416 phosphorylation as a GluA2-binding switch, and established ICA1L as the testis BAR partner.

    Evidence SAXS and cross-linking; in vitro kinase/mutagenesis with imaging for Ser416; ICA1L CRISPR KO with Co-IP and sperm phenotyping

    PMID:26073603 PMID:26306493 PMID:26472923

    Open questions at the time
    • SAXS model lacks high-resolution validation and functional confirmation
    • In vivo significance of Ser416 phosphorylation not demonstrated
  19. 2017 High

    Directly connected PICK1 to the core endocytic machinery, showing NMDAR-dependent AP2 and dynamin interactions that cluster AMPARs at endocytic zones and stimulate dynamin polymerization.

    Evidence Co-IP, in vitro dynamin polymerization, superresolution microscopy, NMDAR-stimulated internalization

    PMID:28855251

    Open questions at the time
    • Temporal coordination of AP2/dynamin recruitment with BAR/actin activity not resolved
    • Selectivity for endocytic versus retention steps incompletely mapped
  20. 2018 High

    Identified an N-terminal amphipathic helix as the BAR curvature-sensing element controlling PICK1 density on high-curvature granules during insulin granule maturation, linking curvature sensing to hormone storage.

    Evidence Liposome curvature assays, super-resolution imaging, mutagenesis in INS-1E cells

    PMID:29768204

    Open questions at the time
    • Whether the same helix governs synaptic curvature sensing not tested
    • Downstream secretory consequences quantified only in one cell model

Open questions

Synthesis pass · forward-looking unresolved questions
  • How PICK1's regulatory inputs (Ca2+ binding, palmitoylation, phosphorylation, ubiquitination, BAR oligomerization/autoinhibition, and competing partners Arf1/NCS-1/ICA proteins) are integrated into an ordered conformational cycle during a single trafficking or plasticity event remains unresolved.
  • No full-length structure or time-resolved model of the PDZ–linker–BAR conformational cycle
  • Quantitative ordering of endocytosis, retention, actin and curvature steps in live neurons lacking
  • Integration of synaptic and secretory/endocrine roles into a unified mechanism not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 7 GO:0008289 lipid binding 4 GO:0098772 molecular function regulator activity 4 GO:0008092 cytoskeletal protein binding 2 GO:0140299 molecular sensor activity 2
Localization
GO:0005768 endosome 3 GO:0005886 plasma membrane 3 GO:0031410 cytoplasmic vesicle 3 GO:0005794 Golgi apparatus 2 GO:0005856 cytoskeleton 2
Pathway
R-HSA-112316 Neuronal System 4 R-HSA-5653656 Vesicle-mediated transport 4 R-HSA-9609507 Protein localization 3 R-HSA-162582 Signal Transduction 2 R-HSA-1852241 Organelle biogenesis and maintenance 2
Partners
ARF1DNM1GRIA2GRM7ICA1LICA69PRKCASLC6A3
Complex memberships
PICK1-ICA1L BAR heterodimerPICK1-ICA69 BAR heterodimer

Evidence

Reading pass · 53 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 PICK1 was identified as a protein that interacts specifically with the catalytic domain of PKCα via yeast two-hybrid screening; PICK1 is an efficient substrate for phosphorylation by PKC in vitro and in vivo, and is localized to the perinuclear region where it becomes phosphorylated upon PKC activation. Yeast two-hybrid, in vitro/in vivo phosphorylation assay, subcellular localization The Journal of cell biology High 7844141
1997 PICK1 contains a PDZ domain that binds specifically to the C-terminal PDZ-binding motif (QSAV) of PKCα; mutation of the carboxylate-binding loop of the PICK1 PDZ domain abolishes this interaction. PICK1 also homooligomerizes through sequences distinct from the carboxylate-binding loop, and a C. elegans PICK1-like protein also binds PKCα, indicating evolutionary conservation. Mutagenesis, GST pulldown, yeast two-hybrid The Journal of biological chemistry High 9405395
1999 PICK1 interacts with the C termini of AMPA receptor subunits (GluR1-4 short splice variants) via its PDZ domain in vitro and in vivo; in neurons, PICK1 colocalizes with AMPA receptors at excitatory synapses and induces their clustering in heterologous expression systems. Co-immunoprecipitation, GST pulldown, immunofluorescence, heterologous expression clustering assay Neuron High 10027300
1999 The PICK1 PDZ domain interacts with the C-terminal short splice variants of AMPA receptor subunits via a novel PDZ binding motif (ESVIK I); the long splice variants lacking this motif do not interact. Mutation of Lys-27 in the PICK1 PDZ domain abolishes interaction with GluR2 (and also PKCα binding), indicating both ligands compete for the same domain. Yeast two-hybrid, GST pulldown, Co-immunoprecipitation, co-expression in COS cells Neuropharmacology High 10340301
2001 PICK1 binds PKCα in neurons and heterologous cells in an activation-dependent manner; TPA-induced PICK1–PKCα complexes are co-targeted with PICK1–GluR2 complexes to dendritic spines, where PKC phosphorylates GluR2 on Ser880. PICK1 reduces plasma membrane levels of GluR2, consistent with PKC-facilitated release of GluR2 from synaptic anchors ABP and GRIP and PICK1-dependent transport of GluR2 from the synaptic membrane. Co-immunoprecipitation, immunofluorescence in neurons, surface biotinylation The Journal of neuroscience High 11466413
2001 PICK1 interacts with the dopamine transporter (DAT) via its PDZ domain in vitro and in vivo; coexpression of PICK1 with DAT leads to co-clustering and increases DAT uptake activity by increasing plasma membrane DAT levels. Deletion of the DAT PDZ-binding C-terminus abolishes PICK1 association and impairs DAT localization in neurons. Co-immunoprecipitation, colocalization imaging, [3H]dopamine uptake assay, deletion mutagenesis Neuron High 11343649
2001 PICK1 interacts with BNaC1 (ASIC2) and BNaC2 (ASIC1) via its PDZ domain; coexpression leads to clustering of these channels in intracellular compartments. PICK1 and BNaC1α colocalize at peripheral mechanosensory endings of DRG neurons. Yeast two-hybrid, GST pulldown, co-immunoprecipitation, immunofluorescence The Journal of biological chemistry Medium 11739374
2000 PICK1 interacts with the C-terminus of mGluR7a via its PDZ domain in vitro and in vivo; PICK1 forms a trimeric complex with mGluR7a and PKCα in COS-7 cells. PICK1 reduces PKCα-evoked phosphorylation of mGluR7a in in vitro phosphorylation assays. Yeast two-hybrid, GST pulldown, co-immunoprecipitation, in vitro kinase assay The Journal of neuroscience High 11007882
2000 Presynaptic clustering of mGluR7a requires its PDZ-binding C-terminus and the PICK1 PDZ domain; coexpression in heterologous cells induces coclustering, and deletion of the PICK1 binding site targets mGluR7a to axons without clustering at presynaptic sites. Heterologous expression clustering assay, immunofluorescence in neurons, deletion mutagenesis Neuron High 11144358
2000 The PDZ domain of PICK1 interacts with constitutively active (GTP-bound) ARF1 and ARF3 but not GDP-bound ARFs or ARF5/6; the interaction requires the PDZ domain of PICK1 and the extreme C-terminus of ARF1. Yeast two-hybrid, deletion mutagenesis Biochemical and biophysical research communications Medium 10623590
2002 NSF ATPase activity, together with α-/β-SNAPs, disassembles the GluR2–PICK1 complex; GluR2, PICK1, NSF, and SNAPs form a complex in the presence of ATPγS. SNAP overexpression in hippocampal neurons produces changes in AMPAR trafficking by acting on GluR2–PICK1 complexes, demonstrating that NSF-mediated synaptic stabilization of AMPARs involves disruption of GluR2–PICK1 interactions. Biochemical complex formation, ATPase activity assay, co-immunoprecipitation, neuronal overexpression Neuron High 11931741
2002 PICK1 interaction with the PDZ-binding C-terminus of ASIC2a is required for PKC-dependent potentiation (~300%) of ASIC2a currents; PICK1 directly scaffolds PKCα to phosphorylate ASIC2a at a major site on its N-terminus (TIR motif at position 39), as demonstrated by 32P labeling and immunoprecipitation. Electrophysiology, 32P phosphate labeling, immunoprecipitation, mutagenesis The Journal of biological chemistry High 12399460
2002 PICK1 is required for mGluR7a-mediated inhibition of P/Q-type Ca2+ channels and mGluR7a-dependent inhibition of synaptic transmission in cerebellar granule neurons; the mGluR7a–PICK1 PDZ interaction is necessary for these signaling functions. Electrophysiology in cultured cerebellar neurons, dominant-negative PDZ peptide interference The EMBO journal Medium 12065412
2003 PICK1 localizes to mitochondria (not ER or Golgi) in NIH 3T3 cells via its PDZ domain; upon serum stimulation, PICK1 recruits activated PKCα to mitochondria in a direct PICK1–PKCα interaction-dependent manner. TPA stimulation, by contrast, drives PKCα to the plasma membrane independently of PICK1. Immunofluorescence with organelle markers, deletion/mutation constructs, subcellular fractionation The Journal of biological chemistry Medium 12826667
2004 A specific K27E mutation in the PICK1 PDZ carboxylate-binding loop abolishes interaction with GluR2 (type II PDZ ligand) but retains interaction with PKCα (type I PDZ ligand), demonstrating that the PDZ domain of PICK1 has distinct binding subsites for PKCα and GluR2. GST pulldown, co-immunoprecipitation, heterologous cell clustering assay, mutagenesis The Journal of biological chemistry High 15247289
2005 The PICK1 PDZ domain binds type II ligands (e.g., DAT C-terminus: WLKV) with ~15-fold higher affinity than type I ligands (PKCα: QSAV) and >100-fold higher than beta2-adrenergic receptor (DSLL); Lys83 in the αB1 position of the PDZ domain mimics hydrophobic residues of type II PDZ domains. The P0 position preference is Val > Ile > Leu. Fluorescence polarization binding assay, mutagenesis, molecular modeling The Journal of biological chemistry High 15774468
2005 PICK1 is a Ca2+-binding protein; PICK1–GluR2 interactions are enhanced by 15 µM Ca2+. Deletion of an N-terminal acidic domain reduces Ca2+ binding and renders the GluR2–PICK1 interaction Ca2+-insensitive. Overexpression of this Ca2+-insensitive PICK1 mutant occludes NMDA-induced AMPAR internalization in hippocampal neurons. Ca2+ binding assay, co-immunoprecipitation in presence of Ca2+, neuronal overexpression with NMDA stimulation The EMBO journal High 16138078
2005 GluR2-interacting proteins PICK1 and NSF are specifically required for calcium-permeable AMPA receptor plasticity (CARP); PICK1 but not NSF regulates the formation of extrasynaptic plasma membrane pools of GluR2-containing receptors that are laterally mobilized into synapses during CARP. Electrophysiology, surface biotinylation, genetic knockout/knockdown in neurons Neuron High 15797551
2006 PICK1 directly binds phosphoinositide lipids via its BAR domain; lipid binding is positively regulated by the PDZ domain and negatively regulated by the C-terminal acidic domain. BAR domain mutations eliminating lipid binding reduce synaptic targeting of PICK1, abolish AMPA receptor clustering, and impair LTD in hippocampal neurons. Lipid binding assay (liposome), mutagenesis, immunofluorescence, electrophysiology (LTD) The Journal of neuroscience High 16510715
2006 Targeted mutation of the PICK1 PDZ domain or BAR domain (lipid-binding deficient) abolishes cerebellar LTD; LTD in PICK1 knockout Purkinje cells can be rescued by wild-type PICK1 but not PDZ or BAR domain mutants, demonstrating both domains are required for LTD expression. Genetic knockout mouse, rescue transfection with PICK1 mutants, electrophysiology Neuron High 16543133
2005 The PICK1 BAR domain interacts intermolecularly with the ABP/GRIP linker II region and intramolecularly with the PICK1 PDZ domain. Binding of PKCα or GluR2 to the PICK1 PDZ domain disrupts the intramolecular interaction and facilitates PICK1 BAR domain association with ABP/GRIP. Disruption of the PICK1–ABP/GRIP interaction impairs GluR2 S880 phosphorylation by PKC and decreases constitutive GluR2 surface expression, NMDA-induced GluR2 endocytosis, and GluR2 recycling. Co-immunoprecipitation, GST pulldown, surface biotinylation, live cell imaging Neuron High 16055064
2007 Parkin (an E3 ubiquitin ligase) binds PICK1 via a PDZ-mediated interaction and promotes monoubiquitination of PICK1 rather than polyubiquitination. Parkin does not promote PICK1 degradation, but wild-type parkin (not PDZ-binding or E3 ligase-defective mutants) abolishes PICK1-dependent PKC-induced potentiation of ASIC2a currents; loss of parkin in knockout neurons unmasks ASIC current potentiation normally suppressed by endogenous parkin. Co-immunoprecipitation, ubiquitination assay, electrophysiology in parkin KO neurons Molecular biology of the cell High 17553932
2007 The PICK1 PDZ domain can directly interact with lipid membranes through a polybasic amino acid cluster and a conserved Cys-Pro-Cys (CPC) motif located away from the peptide ligand-binding groove. Disruption of this PDZ–lipid interaction abolishes synaptic targeting of PICK1. Mutation of the CPC motif does not affect PICK1–GluR2 interaction but eliminates PICK1-induced GluR2 clustering and AMPA receptor trafficking in neurons. Lipid binding assay, mutagenesis, immunofluorescence in neurons The EMBO journal High 17914463
2007 Crystal structure of the PICK1 PDZ domain was determined; self-binding C-terminal extensions mimicking ligand C-termini were used to obtain crystal contacts consistent with canonical class I and class II PDZ–ligand interactions. X-ray crystallography Protein science Medium 17384233
2007 ICA69 (islet cell autoantigen 69 kDa) is identified as the major BAR-domain binding partner of PICK1 in brain; over three-quarters of ICA69 and PICK1 associate together. ICA69–PICK1 heteromeric BAR domain complexes bind lipid membranes. ICA69 is absent from synapses (where PICK1 is enriched) and its overexpression redistributes PICK1 away from synapses and disrupts PICK1-induced AMPA receptor clustering, reducing synaptic targeting and surface expression of AMPARs. Co-immunoprecipitation, liposome binding assay, immunofluorescence, surface expression assay The Journal of neuroscience High 18032668
2008 PICK1 binds filamentous (F)-actin and the actin-nucleating Arp2/3 complex and potently inhibits Arp2/3-mediated actin polymerization. RNAi knockdown of PICK1 in neurons causes cytoskeletal reorganization and aberrant morphology. A PICK1 W413A mutant that cannot bind or inhibit Arp2/3 does not rescue the morphology phenotype and blocks NMDA-induced AMPAR internalization. In vitro actin polymerization assay, pulldown (F-actin/Arp2/3), RNAi knockdown with morphology readout, NMDA-induced internalization assay Nature cell biology High 18297063
2008 PICK1 is a calcium-sensing PDZ domain protein required for bidirectional NMDAR-dependent synaptic plasticity (LTP and LTD) in hippocampal CA1 neurons; PICK1 overexpression potentiates AMPAR-mediated transmission via NMDAR- and CaMK/PKC-dependent mechanisms, and blockade of PICK1 PDZ interactions or PICK1 deletion prevents both LTP and LTD. Electrophysiology (LTP/LTD), PICK1 KO mice, viral PICK1 overexpression, PDZ-blocking peptides Neuron High 18367088
2008 Disruption of the mGluR7a–PICK1 PDZ interaction (via dominant-negative peptide or targeted mGluR7a C-terminus mutation) causes absence-like seizures and EEG spike-and-wave discharges in rats and mice; Pick1 gene inactivation also facilitates pharmacological induction of absence epilepsy. Cell-permeant peptide injection, targeted mGluR7a mutation, Pick1 gene knockout, EEG recording Nature neuroscience High 18641645
2008 Membrane localization is required for activation of the PICK1 BAR domain: in the absence of a membrane-localized PDZ ligand, the BAR domain is auto-inhibited through a PDZ-domain- and linker-dependent mechanism. Localization of PICK1 to membrane (via myristoylation or transmembrane PDZ ligand) activates BAR domain-dependent clustering independently of ligand binding per se. Truncation and mutation constructs, live-cell imaging, colocalization with endosomal markers Traffic Medium 18466293
2008 mGluR-LTD (but not NMDAR-LTD) requires the neuronal Ca2+ sensor NCS-1, which binds directly to the PICK1 BAR domain in a Ca2+-dependent manner; NCS-1–PICK1 association is stimulated by mGluR activation. Introduction of a PICK1 BAR domain fusion protein specifically blocks mGluR-LTD. Co-immunoprecipitation, electrophysiology (LTD), BAR domain fusion protein interference Neuron High 19109914
2008 PICK1 interacts with PKCα and GLT1b (glutamate transporter splice variant) via its PDZ domain; the interaction requires the PICK1-binding C-terminal residues of GLT1b. PICK1–GLT1b interaction regulates PKC-dependent modulation of glutamate transport: blocking this interaction with a decoy peptide renders neuronal glutamate transport responsive to phorbol ester (PKC activation). Yeast two-hybrid, co-immunoprecipitation, fluorescence polarization, decoy peptide functional assay The European journal of neuroscience Medium 18184314
2009 PICK1 is required for acrosome formation during spermiogenesis; PICK1-deficient male mice show fragmentation of proacrosomal granules leading to globozoospermia. PICK1 interacts with GOPC and CK2α' (whose deficiencies also cause globozoospermia) and localizes to Golgi-derived proacrosomal granules. GOPC colocalizes with PICK1 in the Golgi and facilitates PICK1-positive cluster formation. Knockout mouse, immunofluorescence, co-immunoprecipitation, electron microscopy The Journal of clinical investigation High 19258705
2007 PICK1 and mGluR7 surface expression are co-regulated: PKC phosphorylation of mGluR7 on Ser862 inhibits calmodulin binding, increases mGluR7 surface expression, and increases binding to PICK1. In PICK1 knockout mice, PKC-dependent increases in mGluR7 phosphorylation and surface expression are diminished, and mGluR7-dependent plasticity at hippocampal mossy fiber–interneuron synapses is impaired. PICK1 KO mouse, surface biotinylation, phosphorylation assay, electrophysiology Neuron High 18549785
2010 Calcium binding to the N-terminal acidic motif of PICK1 is essential for intracellular retention of internalized AMPARs underlying hippocampal NMDAR-dependent LTD. PICK1 does not regulate initial NMDAR-induced AMPAR endocytosis but is required for keeping internalized receptors intracellular. Mutations disrupting Ca2+-induced structural changes in PICK1 preclude LTD. shRNA knockdown and rescue with PICK1 mutants, AMPAR trafficking assay (pH-sensitive GFP), electrophysiology The Journal of neuroscience High 21147983
2009 FSC231, a small-molecule inhibitor of the PICK1 PDZ domain, inhibits PICK1–GluR2 co-immunoprecipitation, accelerates GluR2 recycling after NMDAR-induced internalization, and blocks both LTP and LTD expression in hippocampal CA1 neurons. The binding mode was identified by mutational analysis and docking against the PDZ domain structure. Fluorescence polarization screening, Co-IP, pHluorin-GluR2 recycling assay, electrophysiology PNAS High 20018661
2011 PICK1 inhibits Arp2/3-mediated actin polymerization to regulate dendritic spine size: PICK1 knockdown increases spine size and PICK1 overexpression decreases spine size. NMDAR-induced spine shrinkage is blocked by PICK1 knockdown or by a PICK1 mutant unable to bind Arp2/3. PICK1–Arp2/3 interaction is required for hippocampal LTD. RNAi knockdown, overexpression with mutants, spine imaging, electrophysiology (LTD) The EMBO journal High 21252856
2011 PICK1 loss of function occludes homeostatic synaptic scaling (inactivity-induced increase in surface AMPARs): chronic activity blockade reduces PICK1 protein levels coinciding with AMPAR accumulation; PICK1 KO neurons show altered GluA2-containing AMPAR subunit composition and abundance, and fail to upscale in response to inactivity. PICK1 KO neurons, chronic TTX/bicuculline treatment, surface biotinylation, electrophysiology The Journal of neuroscience High 21307255
2012 PICK1 interacts with all three PACSIN family members (PACSIN1, 2, 3) and forms a complex with AMPARs; PICK1–PACSIN interaction is regulated by PACSIN phosphorylation. Knockdown of PACSIN1 reduces AMPAR internalization after NMDAR activation. Genetic deletion of PACSIN2 eliminates cerebellar LTD, rescuable by wild-type PACSIN2 but not by a phosphomimetic PACSIN2 that does not bind PICK1. Co-immunoprecipitation, PACSIN2 KO mouse, electrophysiology, internalization assay PNAS High 23918399
2013 Arf1-GTP binds PICK1 and limits PICK1-mediated inhibition of Arp2/3, thereby regulating surface GluA2 levels and spine size. NMDAR stimulation downregulates Arf1 activation (via the Arf-GAP GIT1) and its binding to PICK1, releasing PICK1-Arp2/3 inhibition to enable AMPAR internalization and spine shrinkage underlying LTD. Co-immunoprecipitation, Arf1 mutant expression, surface GluA2 assay, spine imaging, electrophysiology Neuron High 23889934
2013 PICK1 is required for biogenesis of secretory vesicles (immature secretory vesicles/dense-core vesicles) from the trans-Golgi network in endocrine/neuroendocrine cells; PICK1-deficient mice and Drosophila show growth retardation, decreased GH and insulin storage, and reduced secretory vesicle number. PICK1 BAR domain membrane-sculpting activity is demonstrated in vitro, and PICK1 deficiency abolishes ICA69 expression. Knockout mouse, electron microscopy, live imaging of TGN vesicle budding, in vitro membrane tubulation assay, co-immunoprecipitation PLoS biology High 23630454
2013 DHHC8 palmitoylates PICK1 at a cysteine residue essential for cerebellar LTD. DHHC8 binds PICK1, and DHHC8 knockout or prevention of PICK1 palmitoylation prevents LTD induction in Purkinje neurons. Palmitoylation assay, co-immunoprecipitation, DHHC8 KO mouse, electrophysiology The Journal of neuroscience High 24068808
2012 PICK1 promotes caveolin-dependent degradation of TGF-β type I receptor (TβRI) by directly interacting with the TβRI C-terminus via its PDZ domain, scaffolding TβRI to caveolin-1, enhancing caveolae localization, and increasing caveolin-mediated endocytosis, ubiquitination, and degradation of TβRI, thereby antagonizing TGF-β signaling. Co-immunoprecipitation, ubiquitination assay, lipid raft fractionation, TGF-β signaling assay (Smad phosphorylation) Cell research High 22710801
2012 PICK1 reduces the reinsertion rate of PDZ-binding partners sorted to Rab11-dependent slow recycling compartments in a BAR and PDZ domain-dependent manner, as shown using engineered chimeric receptors in HEK293 cells with inducible PICK1 expression. ELISA-based surface trafficking assay, confocal microscopy, inducible expression system The Journal of biological chemistry Medium 22303009
2014 GluA2 trafficking from the endoplasmic reticulum to the plasma membrane requires Ca2+ release from internal stores (via IP3/ryanodine receptors), CaMKII activity, and PICK1 interaction with GluA2. CaMKII enters a complex containing PICK1 (dependent on PICK1 BAR domain) upon Ca2+ release and stimulates GluA2 ER exit and surface trafficking. Co-immunoprecipitation, surface biotinylation, pharmacological inhibition, neuronal biochemistry The Journal of biological chemistry Medium 24831007
2014 PICK1 promotes Ago2 localization at endosomal compartments in neuronal dendrites via a novel direct interaction between PICK1 and Ago2; PICK1 inhibits Ago2-mediated translational repression following neuronal stimulation. Co-immunoprecipitation, colocalization imaging, reporter assay for translational repression EMBO reports Medium 24723684
2014 NMR spectroscopy and mutagenesis reveal three structural binding modes for the PICK1 PDZ domain: type II ligands (e.g., DAT) use canonical binding; type I ligands (e.g., PKCα) depend on residues upstream of the canonical C-terminal binding sequence; ASIC1a uses a dual binding mode with both canonical and non-canonical internal insertion. Evolutionary analysis supports these unconventional modes as evolved expansions of PDZ binding specificity. NMR spectroscopy, mutagenesis, fluorescence polarization, molecular modeling The Journal of biological chemistry High 25023278
2015 Small-angle X-ray scattering (SAXS) reveals that PICK1 forms dimeric and tetrameric complexes in solution via an offset, parallel BAR–BAR oligomerization mode; the PDZ domains are flexibly positioned relative to the BAR dimer, enabling long-range dynamic scaffolding. BAR oligomerization is proposed to mediate BAR domain auto-inhibition. Small-angle X-ray scattering (SAXS), biochemical cross-linking Structure Medium 26073603
2015 ICA1L (ICA69-like) is the major BAR-domain binding partner of PICK1 in testis; ICA1L and PICK1 are co-expressed in spermatids and co-trafficked during spermiogenesis. ICA1L knockout mice show PICK1 expression reduced by 80% in testes and exhibit globozoospermia-like defects. Co-immunoprecipitation, ICA1L KO mouse (CRISPR-Cas), immunofluorescence, sperm phenotyping Journal of cell science High 26306493
2015 GSK-3β phosphorylates PICK1 at Ser416 in its C-terminal region; Ser416 phosphorylation is required for PICK1–GluA2 interaction. Ser416-to-Ala substitution disrupts GluA2–PICK1 interaction and increases PICK1 membrane association (cluster formation), while Ser416Glu/Asp substitution retains interaction. This GSK-3β-mediated phosphorylation of PICK1 is proposed to regulate LTD. In vitro kinase assay, co-immunoprecipitation, mutagenesis, live cell imaging The Journal of biological chemistry Medium 26472923
2017 PICK1 makes direct, NMDAR-dependent interactions with core endocytic proteins AP2 (α-appendage) and dynamin. PICK1–AP2 interactions are required for clustering AMPARs at endocytic zones in response to NMDAR stimulation and for consequent AMPAR internalization. PICK1 also stimulates dynamin polymerization in vitro. Co-immunoprecipitation, in vitro dynamin polymerization assay, superresolution microscopy, NMDAR stimulation internalization assay The Journal of cell biology High 28855251
2018 An amphipathic helix N-terminal to the PICK1 BAR domain mediates membrane curvature sensing (MCS). Mutational disruption of this helix impairs MCS without affecting membrane binding per se and selectively reduces PICK1 density on high-curvature insulin granules during their maturation in INS-1E cells, reducing hormone storage. Super-resolution microscopy, liposome curvature assay, mutagenesis, cell biology in INS-1E cells Cell reports High 29768204
2014 PICK1 BAR domain controls vesicle number and size in adrenal chromaffin cells: PICK1 KO reduces large dense-core vesicle (LDCV) number and quantal size without affecting fusion kinetics. BAR domain lipid-binding mutations (2K-E) and PDZ domain lipid-binding mutations (CC-GG) each reproduce the secretion phenotype of null mutant, indicating a conserved mechanism. PICK1 KO mouse, electron microscopy, amperometry/capacitance exocytosis assay, viral rescue, mutagenesis The Journal of neuroscience High 25100601
2016 PICK1 forms a functional complex with ASIC1 and calcineurin in pulmonary arterial smooth muscle cells; PICK1 is required downstream of ASIC1-mediated Ca2+ influx for NFATc3 nuclear import. Inhibition of PICK1 (FSC231) abolishes ET-1- and ionomycin-induced NFATc3 nuclear import without altering Ca2+ responses. Proximity ligation assay (PLA), ASIC1 KO mice, pharmacological inhibition, NFATc3 nuclear import assay American journal of physiology. Lung cellular and molecular physiology Medium 27190058

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 Clustering of AMPA receptors by the synaptic PDZ domain-containing protein PICK1. Neuron 486 10027300
2001 PICK1 targets activated protein kinase Calpha to AMPA receptor clusters in spines of hippocampal neurons and reduces surface levels of the AMPA-type glutamate receptor subunit 2. The Journal of neuroscience : the official journal of the Society for Neuroscience 274 11466413
1995 PICK1: a perinuclear binding protein and substrate for protein kinase C isolated by the yeast two-hybrid system. The Journal of cell biology 267 7844141
2001 Functional interaction between monoamine plasma membrane transporters and the synaptic PDZ domain-containing protein PICK1. Neuron 260 11343649
2006 Targeted in vivo mutations of the AMPA receptor subunit GluR2 and its interacting protein PICK1 eliminate cerebellar long-term depression. Neuron 244 16543133
2005 Calcium-permeable AMPA receptor plasticity is mediated by subunit-specific interactions with PICK1 and NSF. Neuron 212 15797551
1997 Specific interaction of the PDZ domain protein PICK1 with the COOH terminus of protein kinase C-alpha. The Journal of biological chemistry 207 9405395
2005 PICK1 interacts with ABP/GRIP to regulate AMPA receptor trafficking. Neuron 187 16055064
1999 The protein kinase C alpha binding protein PICK1 interacts with short but not long form alternative splice variants of AMPA receptor subunits. Neuropharmacology 179 10340301
2008 Inhibition of Arp2/3-mediated actin polymerization by PICK1 regulates neuronal morphology and AMPA receptor endocytosis. Nature cell biology 178 18297063
2003 Rapid and differential regulation of AMPA and kainate receptors at hippocampal mossy fibre synapses by PICK1 and GRIP. Neuron 174 12597860
2002 NSF ATPase and alpha-/beta-SNAPs disassemble the AMPA receptor-PICK1 complex. Neuron 165 11931741
2009 PICK1 deficiency causes male infertility in mice by disrupting acrosome formation. The Journal of clinical investigation 161 19258705
2004 Regulation of synaptic strength and AMPA receptor subunit composition by PICK1. The Journal of neuroscience : the official journal of the Society for Neuroscience 153 15190111
2007 PICK1 and phosphorylation of the glutamate receptor 2 (GluR2) AMPA receptor subunit regulates GluR2 recycling after NMDA receptor-induced internalization. The Journal of neuroscience : the official journal of the Society for Neuroscience 149 18077702
2008 An essential role for PICK1 in NMDA receptor-dependent bidirectional synaptic plasticity. Neuron 146 18367088
2005 PICK1 is a calcium-sensor for NMDA-induced AMPA receptor trafficking. The EMBO journal 136 16138078
2000 PICK1 interacts with and regulates PKC phosphorylation of mGLUR7. The Journal of neuroscience : the official journal of the Society for Neuroscience 133 11007882
2000 Presynaptic clustering of mGluR7a requires the PICK1 PDZ domain binding site. Neuron 124 11144358
2006 Lipid binding regulates synaptic targeting of PICK1, AMPA receptor trafficking, and synaptic plasticity. The Journal of neuroscience : the official journal of the Society for Neuroscience 121 16510715
2002 The PDZ proteins PICK1, GRIP, and syntenin bind multiple glutamate receptor subtypes. Analysis of PDZ binding motifs. The Journal of biological chemistry 120 11891216
2007 Parkin-mediated monoubiquitination of the PDZ protein PICK1 regulates the activity of acid-sensing ion channels. Molecular biology of the cell 119 17553932
2008 PICK1: a multi-talented modulator of AMPA receptor trafficking. Pharmacology & therapeutics 109 18353440
2001 The PDZ domain protein PICK1 and the sodium channel BNaC1 interact and localize at mechanosensory terminals of dorsal root ganglion neurons and dendrites of central neurons. The Journal of biological chemistry 109 11739374
2010 A newly discovered mutation in PICK1 in a human with globozoospermia. Asian journal of andrology 102 20562896
2009 Identification of a small-molecule inhibitor of the PICK1 PDZ domain that inhibits hippocampal LTP and LTD. Proceedings of the National Academy of Sciences of the United States of America 101 20018661
2006 Serine racemase binds to PICK1: potential relevance to schizophrenia. Molecular psychiatry 101 16314870
2010 Calcium binding to PICK1 is essential for the intracellular retention of AMPA receptors underlying long-term depression. The Journal of neuroscience : the official journal of the Society for Neuroscience 99 21147983
2002 Interaction of the synaptic protein PICK1 (protein interacting with C kinase 1) with the non-voltage gated sodium channels BNC1 (brain Na+ channel 1) and ASIC (acid-sensing ion channel). The Biochemical journal 98 11802773
2002 Protein kinase C stimulates the acid-sensing ion channel ASIC2a via the PDZ domain-containing protein PICK1. The Journal of biological chemistry 96 12399460
2007 Structure and function of PICK1. Neuro-Signals 92 17215589
2011 PICK1 loss of function occludes homeostatic synaptic scaling. The Journal of neuroscience : the official journal of the Society for Neuroscience 91 21307255
2009 PICK1-mediated GluR2 endocytosis contributes to cellular injury after neuronal trauma. Cell death and differentiation 91 19644508
2008 Metabotropic glutamate receptor-mediated LTD involves two interacting Ca(2+) sensors, NCS-1 and PICK1. Neuron 91 19109914
2004 ASIC2b-dependent regulation of ASIC3, an essential acid-sensing ion channel subunit in sensory neurons via the partner protein PICK-1. The Journal of biological chemistry 84 14976185
2001 The ERBB2/HER2 receptor differentially interacts with ERBIN and PICK1 PSD-95/DLG/ZO-1 domain proteins. The Journal of biological chemistry 82 11278603
2008 PICK1 uncoupling from mGluR7a causes absence-like seizures. Nature neuroscience 81 18641645
2013 The small GTPase Arf1 modulates Arp2/3-mediated actin polymerization via PICK1 to regulate synaptic plasticity. Neuron 77 23889934
2011 PICK1 inhibition of the Arp2/3 complex controls dendritic spine size and synaptic plasticity. The EMBO journal 77 21252856
2007 PICK1-ICA69 heteromeric BAR domain complex regulates synaptic targeting and surface expression of AMPA receptors. The Journal of neuroscience : the official journal of the Society for Neuroscience 74 18032668
2010 Developmental regulation of protein interacting with C kinase 1 (PICK1) function in hippocampal synaptic plasticity and learning. Proceedings of the National Academy of Sciences of the United States of America 73 21106762
2005 Molecular determinants for the complex binding specificity of the PDZ domain in PICK1. The Journal of biological chemistry 72 15774468
2001 N-methyl-D-aspartate-induced alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA) receptor down-regulation involves interaction of the carboxyl terminus of GluR2/3 with Pick1. Ligand-binding studies using Sindbis vectors carrying AMPA receptor decoys. The Journal of biological chemistry 71 11498531
2013 PICK1 deficiency impairs secretory vesicle biogenesis and leads to growth retardation and decreased glucose tolerance. PLoS biology 69 23630454
2007 Clustering and synaptic targeting of PICK1 requires direct interaction between the PDZ domain and lipid membranes. The EMBO journal 69 17914463
2002 PICK1 is required for the control of synaptic transmission by the metabotropic glutamate receptor 7. The EMBO journal 69 12065412
2013 PICK1 interacts with PACSIN to regulate AMPA receptor internalization and cerebellar long-term depression. Proceedings of the National Academy of Sciences of the United States of America 67 23918399
2008 Corequirement of PICK1 binding and PKC phosphorylation for stable surface expression of the metabotropic glutamate receptor mGluR7. Neuron 67 18549785
2000 Interaction of the C-terminal tail region of the metabotropic glutamate receptor 7 with the protein kinase C substrate PICK1. The European journal of neuroscience 67 11122333
2009 PICK1-mediated glutamate receptor subunit 2 (GluR2) trafficking contributes to cell death in oxygen/glucose-deprived hippocampal neurons. The Journal of biological chemistry 64 19321442
2017 The TGF-β signalling negative regulator PICK1 represses prostate cancer metastasis to bone. British journal of cancer 62 28697177
2007 Structure of PICK1 and other PDZ domains obtained with the help of self-binding C-terminal extensions. Protein science : a publication of the Protein Society 59 17384233
2013 DHHC8-dependent PICK1 palmitoylation is required for induction of cerebellar long-term synaptic depression. The Journal of neuroscience : the official journal of the Society for Neuroscience 57 24068808
2012 PICK1 mediates transient synaptic expression of GluA2-lacking AMPA receptors during glycine-induced AMPA receptor trafficking. The Journal of neuroscience : the official journal of the Society for Neuroscience 57 22915106
2014 Synapto-depressive effects of amyloid beta require PICK1. The European journal of neuroscience 55 24713001
2017 PICK1 regulates AMPA receptor endocytosis via direct interactions with AP2 α-appendage and dynamin. The Journal of cell biology 54 28855251
2013 The antagonistic modulation of Arp2/3 activity by N-WASP, WAVE2 and PICK1 defines dynamic changes in astrocyte morphology. Journal of cell science 53 23843614
2008 Interaction between the glutamate transporter GLT1b and the synaptic PDZ domain protein PICK1. The European journal of neuroscience 53 18184314
2020 miR-615-3p promotes the epithelial-mesenchymal transition and metastasis of breast cancer by targeting PICK1/TGFBRI axis. Journal of experimental & clinical cancer research : CR 52 32336285
2012 PICK1 promotes caveolin-dependent degradation of TGF-β type I receptor. Cell research 52 22710801
2018 PICK1 deficiency exacerbates sepsis-associated acute lung injury and impairs glutathione synthesis via reduction of xCT. Free radical biology & medicine 50 29471107
2016 Multiple faces of protein interacting with C kinase 1 (PICK1): Structure, function, and diseases. Neurochemistry international 46 26970394
2000 Interaction of the PDZ domain of human PICK1 with class I ADP-ribosylation factors. Biochemical and biophysical research communications 46 10623590
2006 The schizophrenic faces of PICK1. Trends in pharmacological sciences 45 17011050
2008 Membrane localization is critical for activation of the PICK1 BAR domain. Traffic (Copenhagen, Denmark) 43 18466293
2010 PICK1 regulates incorporation of calcium-permeable AMPA receptors during cortical synaptic strengthening. The Journal of neuroscience : the official journal of the Society for Neuroscience 41 20445062
2012 Protein interacting with C kinase 1 (PICK1) reduces reinsertion rates of interaction partners sorted to Rab11-dependent slow recycling pathway. The Journal of biological chemistry 40 22303009
2014 Trafficking of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA) receptor subunit GluA2 from the endoplasmic reticulum is stimulated by a complex containing Ca2+/calmodulin-activated kinase II (CaMKII) and PICK1 protein and by release of Ca2+ from internal stores. The Journal of biological chemistry 38 24831007
2010 Disruption of PICK1 attenuates the function of ASICs and PKC regulation of ASICs. American journal of physiology. Cell physiology 38 20826761
2004 Association study of PICK1 rs3952 polymorphism and schizophrenia. Neuroreport 38 15305146
2010 PDZ binding to the BAR domain of PICK1 is elucidated by coarse-grained molecular dynamics. Journal of molecular biology 37 21050858
2008 Modulation of D-serine levels in brains of mice lacking PICK1. Biological psychiatry 37 18191108
2018 An Amphipathic Helix Directs Cellular Membrane Curvature Sensing and Function of the BAR Domain Protein PICK1. Cell reports 36 29768204
2006 NMDA receptors mediate calcium-dependent, bidirectional changes in dendritic PICK1 clustering. Molecular and cellular neurosciences 36 16406232
2004 The PDZ domain of PICK1 differentially accepts protein kinase C-alpha and GluR2 as interacting ligands. The Journal of biological chemistry 35 15247289
2015 Structure of Dimeric and Tetrameric Complexes of the BAR Domain Protein PICK1 Determined by Small-Angle X-Ray Scattering. Structure (London, England : 1993) 34 26073603
2014 PICK1 links Argonaute 2 to endosomes in neuronal dendrites and regulates miRNA activity. EMBO reports 34 24723684
2014 Protein interacting with C-kinase 1 (PICK1) binding promiscuity relies on unconventional PSD-95/discs-large/ZO-1 homology (PDZ) binding modes for nonclass II PDZ ligands. The Journal of biological chemistry 34 25023278
2005 PICK-1: a scaffold protein that interacts with Nectins and JAMs at cell junctions. FEBS letters 34 15811349
2001 Molecular determinants for PICK1 synaptic aggregation and mGluR7a receptor coclustering: role of the PDZ, coiled-coil, and acidic domains. The Journal of biological chemistry 34 11375398
2018 PICK1 Deficiency Induces Autophagy Dysfunction via Lysosomal Impairment and Amplifies Sepsis-Induced Acute Lung Injury. Mediators of inflammation 33 30402043
2015 ICA1L forms BAR-domain complexes with PICK1 and is crucial for acrosome formation in spermiogenesis. Journal of cell science 33 26306493
2003 PICK1, an anchoring protein that specifically targets protein kinase Calpha to mitochondria selectively upon serum stimulation in NIH 3T3 cells. The Journal of biological chemistry 33 12826667
2007 PICK1 interacts with alpha7 neuronal nicotinic acetylcholine receptors and controls their clustering. Molecular and cellular neurosciences 32 17467288
2015 PICK1 is implicated in organelle motility in an Arp2/3 complex-independent manner. Molecular biology of the cell 31 25657323
2015 Glycogen Synthase Kinase 3β-mediated Phosphorylation in the Most C-terminal Region of Protein Interacting with C Kinase 1 (PICK1) Regulates the Binding of PICK1 to Glutamate Receptor Subunit GluA2. The Journal of biological chemistry 29 26472923
2007 PDZ domain protein-protein interactions: a case study with PICK1. Current topics in medicinal chemistry 29 17266593
2007 Identification of functional polymorphisms in the promoter region of the human PICK1 gene and their association with methamphetamine psychosis. The American journal of psychiatry 29 17606663
2010 PICK1 regulates the trafficking of ASIC1a and acidotoxicity in a BAR domain lipid binding-dependent manner. Molecular brain 28 21176140
2009 PKCgamma-induced trafficking of AMPA receptors in embryonic zebrafish depends on NSF and PICK1. Proceedings of the National Academy of Sciences of the United States of America 28 19366675
2010 Structure-activity relationships of a small-molecule inhibitor of the PDZ domain of PICK1. Organic & biomolecular chemistry 27 20668766
2006 Molecular mechanisms for regulation of AMPAR trafficking by PICK1. Biochemical Society transactions 27 17052230
2008 Protein interacting with C kinase 1 (PICK1) and GluR2 are associated with presynaptic plasma membrane and vesicles in hippocampal excitatory synapses. Neuroscience 26 19071197
2020 A high-affinity, bivalent PDZ domain inhibitor complexes PICK1 to alleviate neuropathic pain. EMBO molecular medicine 25 32352640
2014 The BAR domain protein PICK1 controls vesicle number and size in adrenal chromaffin cells. The Journal of neuroscience : the official journal of the Society for Neuroscience 24 25100601
2016 PICK1 confers anti-inflammatory effects in acute liver injury via suppressing M1 macrophage polarization. Biochimie 23 27157267
2011 Protein interacting with C kinase (PICK1) is a suppressor of spinocerebellar ataxia 3-associated neurodegeneration in Drosophila. Human molecular genetics 23 21949352
2016 ASIC1-mediated calcium entry stimulates NFATc3 nuclear translocation via PICK1 coupling in pulmonary arterial smooth muscle cells. American journal of physiology. Lung cellular and molecular physiology 22 27190058
2013 Functional modulation of the glutamate transporter variant GLT1b by the PDZ domain protein PICK1. The Journal of biological chemistry 22 23697999
2012 The binding affinities of proteins interacting with the PDZ domain of PICK1. Proteins 22 22275068

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