| 2002 |
WAVE1 exists in a heterotetrameric complex with PIR121, Nap125, and HSPC300 that is constitutively inactive; Rac1 and the adapter protein Nck cause dissociation of this complex, releasing active WAVE1-HSPC300 to drive actin nucleation via the Arp2/3 complex. |
Biochemical purification, reconstitution, in vitro actin nucleation assays, mass spectrometry identification of complex components |
Nature |
High |
12181570
|
| 2000 |
WAVE-1 acts as an A-kinase anchoring protein (AKAP) that assembles a multi-kinase scaffold by simultaneously binding cAMP-dependent protein kinase (PKA) and Abelson tyrosine kinase (Abl); the PKA-binding site overlaps a verprolin homology region that interacts with actin, suggesting competitive regulation. The scaffold dynamically translocates to sites of actin reorganization upon PDGF stimulation. |
AKAP screen, Co-immunoprecipitation from HEK-293 cells and brain extracts, mapping studies, immunocytochemistry in Swiss 3T3 fibroblasts |
The EMBO journal |
High |
10970852
|
| 2006 |
Cyclin-dependent kinase 5 (Cdk5) phosphorylates WAVE1 at multiple serine residues (Ser310, Ser397, Ser441) in vitro and in intact mouse neurons, and phosphorylation inhibits WAVE1-dependent Arp2/3 complex-mediated actin polymerization. Loss of WAVE1 function reduces mature dendritic spine density; a dephosphorylation-mimic mutant rescues spine morphology but a phosphorylation-mimic mutant does not. cAMP signaling reduces Cdk5-site phosphorylation and increases spine density in a WAVE1-dependent manner. |
In vitro kinase assay with Cdk5, phosphorylation-mimic and dephosphorylation-mimic mutagenesis, actin polymerization assays, cultured neuron morphology analysis, in vivo mouse studies |
Nature |
High |
16862120
|
| 2005 |
CRMP-2 interacts with the Sra-1/WAVE1 complex and links it to kinesin-1 light chain, mediating anterograde transport of the Sra-1/WAVE1 complex to axonal growth cones. Knockdown of Sra-1 and WAVE1 canceled CRMP-2-induced axon outgrowth and multiple-axon formation; knockdown of CRMP-2 or kinesin-1 delocalized Sra-1 and WAVE1 from growth cone tips. |
Co-immunoprecipitation, RNA interference knockdown, immunofluorescence localization in hippocampal neurons |
Molecular and cellular biology |
High |
16260607
|
| 2003 |
WAVE2 deficiency impairs peripheral ruffle formation, while WAVE1 deficiency specifically impairs dorsal ruffle formation in PDGF-stimulated fibroblasts. WAVE1, but not WAVE2, colocalizes with matrix metalloproteinase MMP-2 in dorsal ruffles, and WAVE1-dependent migration in ECM requires MMP activity. |
Knockout mouse embryonic fibroblasts, PDGF stimulation assays, immunofluorescence colocalization with MMP-2, MMP inhibitor experiments |
Developmental cell |
High |
14536061
|
| 2007 |
WAVE-1 forms a signaling complex with the GTPase-activating protein WRP (WAVE-associated RhoGAP protein); WRP anchoring to WAVE-1 is required for normal dendritic spine density, synaptic plasticity, and cognitive behavior in mice, as shown by gene targeting that disrupts WRP–WAVE-1 interaction. |
Gene targeting in mice, neuronal time-lapse imaging, electrophysiological recordings, behavioral analyses |
The Journal of neuroscience |
High |
17215396
|
| 2006 |
WAVE1 is expressed in oligodendrocytes and localizes to the lamella leading edge; dominant-negative WAVE1 impairs process outgrowth and lamellipodia formation in oligodendrocytes. WAVE1-knockout mice exhibit regional hypomyelination in corpus callosum and optic nerve, with fewer nodes of Ranvier, demonstrating a cell-autonomous role for WAVE1 in oligodendrocyte morphogenesis and CNS myelination. |
Dominant-negative expression, WAVE1-knockout mouse analysis, immunofluorescence localization, electron microscopy of myelin |
The Journal of neuroscience |
High |
16723544
|
| 2003 |
WAVE1 knockout mice display sensorimotor retardation, reduced anxiety, and deficits in hippocampal-dependent learning and memory, establishing that WAVE-1 is required for normal neural functioning and implicating it in the WAVE-1 signaling network relevant to mental retardation phenotypes. |
Targeted gene disruption (knockout) in mice, behavioral testing, hippocampal-dependent memory assays |
Proceedings of the National Academy of Sciences of the United States of America |
High |
12578964
|
| 2008 |
WAVE1 controls depolarization-induced mitochondrial movement into dendritic spines and filopodia. NMDA receptor activation causes degradation of the p35 regulatory subunit of Cdk5, reducing inhibitory phosphorylation of WAVE1, and this dephosphorylation is associated with mitochondrial redistribution and spine morphogenesis. |
Neuronal depolarization assays, WAVE1 expression manipulation, NMDA receptor pharmacology, mitochondrial trafficking imaging |
Proceedings of the National Academy of Sciences of the United States of America |
Medium |
18287015
|
| 2009 |
The purified native human WAVE complex is intrinsically inactive in actin nucleation assays, indicating that the WCA domain is masked at resting state, analogous to WASP proteins; the complex must be recruited and activated at the plasma membrane to drive lamellipodia formation. |
Affinity purification of native WAVE complex from stable human cell line, in vitro Arp2/3-dependent actin polymerization assay |
Cell motility and the cytoskeleton |
High |
19206172
|
| 2013 |
Xenopus Wave1 is present in the oocyte nucleus and is required for transcriptional reprogramming of sperm and somatic nuclei. Nuclear Wave1 binds active transcription components via its WHD domain and contributes to RNA polymerase II activity. Wave1 knockdown in embryos causes abnormal development and defective Hox gene activation. |
Xenopus oocyte microinjection, knockdown experiments, co-immunoprecipitation of Wave1 with transcription components, domain mapping |
Science |
High |
23990560
|
| 2003 |
VEGF stimulation causes WAVE1 to bind p47phox within membrane ruffles; WAVE1 acts as a scaffold recruiting the NADPH oxidase to a complex with Rac1 and PAK1. PAK1 kinase activity is required for p47phox phosphorylation, oxidant production, and ruffle formation. WAVE1 domain-based competition experiments block VEGF-induced ruffling. |
Co-immunoprecipitation, dominant-negative domain expression, NADPH oxidase activity assays, ruffle formation assays in endothelial cells |
The Journal of biological chemistry |
Medium |
12855698
|
| 2009 |
Estradiol (E2) rapidly phosphorylates WAVE1 at Ser310, Ser397, and Ser441 in rat cortical neurons via a Gαi/Gβ → c-Src → Rac1 → Cdk5 signaling cascade, causing WAVE1 redistribution to the cell membrane at sites of dendritic spine formation and triggering local Arp2/3 complex concentration and actin reorganization. Silencing WAVE1 abrogates E2-induced spine increase. |
Phospho-specific antibodies, signaling pathway inhibitors, Rac1/Cdk5 knockdown, immunofluorescence in cortical neurons, spine counting |
Molecular endocrinology |
Medium |
19460862
|
| 2007 |
WAVE1 and pancortin-2 form a protein complex with Bcl-xL at mitochondria in adult cortical neurons following ischemic stroke; this three-protein complex increases Bax mitochondrial association, cytochrome c release, and neuronal apoptosis. In pancortin-null mice, WAVE1–Bcl-xL interaction is diminished and cortical neurons are protected against ischemia. |
Co-immunoprecipitation, subcellular fractionation, pancortin conditional knockout (Cre-loxP), focal ischemia model in mice |
The Journal of neuroscience |
High |
17301160
|
| 2009 |
WAVE1 interacts with mitochondrial Bcl-2 in leukemia cells; depletion of WAVE1 by RNAi causes mitochondrial release of Bcl-2, phosphorylation of ASK1/JNK and Bcl-2, and increases ROS production, leading to increased apoptosis. WAVE1 overexpression confers resistance to drug-induced apoptosis. |
RNA interference, gene transfection, Co-immunoprecipitation, apoptosis assays, ROS measurement |
Leukemia |
Medium |
19890377
|
| 2015 |
The APP intracellular domain (AICD) binds the Wasf1 promoter and negatively regulates WAVE1 transcription. WAVE1 colocalizes with APP in the Golgi apparatus; reducing WAVE1 decreases budding of APP-containing vesicles, reduces cell-surface APP, and thereby lowers Aβ production. WAVE1 reduction in a mouse AD model dramatically reduced Aβ levels and restored memory deficits. |
Chromatin immunoprecipitation (AICD at Wasf1 promoter), Golgi colocalization, APP vesicle budding assays, APP/Aβ ELISA, mouse AD model behavior |
Nature medicine |
High |
26280122
|
| 2015 |
The cannabinoid CB1 receptor assembles with multiple members of the WAVE1 complex and with Rac1 in neurons in vivo; CB1 receptor activation modulates actin polymerization and stability via WAVE1 in growth cones and synaptic spines, causing collapse/retraction. CB1 agonists attenuate activity-dependent dendritic spine remodeling in spinal cord neurons in vivo via the WAVE1 complex. |
In vivo proteomics pull-down from mouse cortex, actin polymerization assays, dendritic spine imaging in vivo, pain behavior assays |
PLoS biology |
High |
26496209
|
| 2011 |
The NYAP family of phosphoproteins (NYAP1, NYAP2, Myosin16/NYAP3) are tyrosine-phosphorylated by Fyn upon Contactin5 stimulation; phosphorylated NYAPs activate PI3K and simultaneously interact with the WAVE1 complex, physically bridging a PI3K–WAVE1 association that regulates actin cytoskeleton remodeling and neuronal morphogenesis. |
Co-immunoprecipitation, tyrosine phosphorylation assays, PI3K activity assays, NYAP gene disruption in mice |
The EMBO journal |
High |
21946561
|
| 2010 |
WAVE1 phosphorylation at Ser310, Ser397, and Ser441 (by Cdk5) can be reversed by protein phosphatase-2A (PP2A) and protein phosphatase-2B (PP2B/calcineurin), acting on different sites in response to D1 dopamine receptor (via cAMP) and NMDA receptor (via Ca2+) signaling respectively, thereby activating WAVE1. |
Phosphatase inhibitor studies, in vitro phosphatase assays, receptor pharmacology in neurons |
Journal of neurochemistry |
Medium |
20403076
|
| 2004 |
WAVE1 undergoes cell-cycle-dependent nuclear localization during fertilization: redistributes from cortex in GV oocytes to cytoplasmic foci in Met II oocytes, then to pronuclei after sperm entry. Nuclear localization is independent of actin/Arp2/3 and nuclear pores but requires dynamic microtubules. Anti-WAVE1 antibodies prevent pronuclear migration. In Met II oocytes WAVE1 associates with PKA regulatory subunit but not Arp2/3; in Met II it also interacts with Arp2/3. |
Immunofluorescence, immunoprecipitation, wheat germ agglutinin microinjection, taxol microtubule stabilization, antibody microinjection |
Developmental biology |
Medium |
15581863
|
| 2004 |
During mammalian spermatogenesis, WAVE1 localizes to the Golgi apparatus in spermatocytes/round spermatids and to the mitochondrial sheath in elongated spermatids and sperm. WAVE1 co-localizes with PKA RII along the mitochondrial sheath, establishing a signaling unit in the sperm midpiece; this distribution is conserved across mouse, bull, baboon, and human. |
Transmission electron microscopy, immunocytochemistry, western blotting across multiple species |
Human reproduction |
Medium |
15471936
|
| 2007 |
WAVE1 plays a major role downstream of the GPVI collagen receptor in platelets: WAVE1-knockout platelets show markedly inhibited lamellipodia formation on CRP and laminin (GPVI-dependent substrates) and impaired aggregation in response to CRP, while responses to GPCR agonist thrombin are unaffected. |
WAVE1 knockout mouse platelets, lamellipodia formation assays on defined substrates, platelet aggregation assays |
Journal of thrombosis and haemostasis |
High |
17319906
|
| 2013 |
WAVE1 (acting as an AKAP) mediates the suppression of macrophage phagocytosis by oxidized phospholipids (OxPL/DAMPs): OxPL activates an anchored PKA pool, and WAVE1 gene silencing or Wave1-knockout chimeric mice abolish OxPL-induced impairment of phagocytosis and extend survival after E. coli infection. |
RNAi gene silencing, Wave1-knockout chimeric mice, phagocytosis assays, in vivo bacterial infection model |
The Journal of clinical investigation |
High |
23934128
|
| 2018 |
De novo heterozygous truncating mutations in WASF1 (WAVE1) that partially or fully disrupt the C-terminal WCA actin-binding domain cause intellectual disability with seizures. Functional studies in patient fibroblasts confirmed truncated WASF1 protein and a defect in actin remodeling. |
Exome/whole-genome sequencing of patients, Western blot for truncated protein in patient fibroblasts, actin remodeling assays in patient cells |
American journal of human genetics |
Medium |
29961568
|
| 2016 |
Retrolinkin interacts with the CYFIP1/2 subunit of the WAVE1 complex; this interaction recruits WAVE1 to the neuronal plasma membrane upon BDNF stimulation and is required for clathrin-independent, actin-dependent endocytosis of activated TrkB and subsequent dendrite outgrowth. N-WASP is not required for this process. |
Co-immunoprecipitation, dominant-negative disruption of retrolinkin–CYFIP1/2 interaction, WAVE1 knockdown, TrkB endocytosis assays, dendrite morphology |
Molecular biology of the cell |
Medium |
27605705
|
| 2005 |
WAVE1 is required for stabilization (but not initial extension) of lamellipodial protrusions during cell spreading on fibronectin: WAVE1-KO MEFs show decreased actin filament density at protrusion tips and increased membrane extension speed, causing focal complex deformation, while WAVE2-KO MEFs fail to form lamellipodial structures. |
Knockout MEFs (WAVE1-KO and WAVE2-KO), live-cell imaging during spreading on fibronectin, actin filament density analysis |
Genes to cells |
Medium |
15836768
|
| 2009 |
ArgBP2 and CIP4 both directly interact with WAVE1 and can enhance its tyrosine phosphorylation catalyzed by c-Abl; ArgBP2 and CIP4 act synergistically to increase WAVE1 tyrosine phosphorylation. However, CIP4 is dispensable for ArgBP2-induced blockade of cell migration. |
Yeast two-hybrid, Co-immunoprecipitation, in vitro kinase assays with c-Abl, cell migration assays |
Cancer letters |
Medium |
19631450
|
| 2004 |
WAVE1 isoform is preferentially precipitated by profilin I (SH3 domain pull-down) compared with WAVE2, while the IRSp53 SH3 domain precipitates WAVE2 more efficiently; the Abl SH3 domain binds all three WAVE isoforms. All three WAVE isoforms are substrates for calpain cleavage in vivo and in vitro in platelets. |
SH3 domain pull-down with platelet lysates, in vitro calpain cleavage assays, Triton X-100 fractionation |
Blood |
Medium |
15280206
|
| 2020 |
WAVE1 and WAVE2 are redundant for lamellipodia formation and motility in B16-F1 melanoma cells; however, WAVE1 KO increases the rate of leading-edge actin extension (while WAVE2 KO decreases it), and WAVE1 restricts actin extension rate and couples actin networks to the membrane to drive protrusion. The faster actin extension in WAVE1-KO cells is offset by increased retrograde flow. |
CRISPR knockout of WAVE1 and WAVE2 individually and together, live-cell imaging of actin dynamics at leading edge, protrusion rate measurements |
Molecular biology of the cell |
High |
32697617
|
| 2015 |
Phosphorylated WAVE1 (p-WAVE1) and phosphorylated CRMP2 co-localize with aggregated hyperphosphorylated tau in hippocampal neurons of triple-transgenic AD model mice and are present in sarkosyl-insoluble fractions; both are phosphorylated by Cdk5 and their phosphorylation correlates with tau aggregate formation. |
Immunofluorescence colocalization, subcellular fractionation (sarkosyl-insoluble), ATRA pharmacological treatment in 3xTg-AD mice |
Journal of neuroscience research |
Low |
26400044
|
| 2021 |
The WAVE complex localizes to regions of saddle membrane curvature as actin-independent 230-nm-wide rings (visualized by super-resolution microscopy); the WAVE complex recruits IRSp53 to saddle curvature sites but does not depend on IRSp53 for its own localization. Sheet-like protrusions persist in ARP2-null cells but not in WAVE complex-null cells, indicating WAVE complex has roles in morphogenesis beyond Arp2/3 activation. |
Super-resolution microscopy, ARP2-null and WAVE complex-null cell lines, curvature analysis, IRSp53 localization |
The Journal of cell biology |
High |
34096975
|