| 1998 |
Nexilin (b-nexilin and s-nexilin) are F-actin binding proteins isolated from rat brain and fibroblasts. b-Nexilin has two F-actin-binding domains (ABDs) at NH2-terminal and middle regions and shows F-actin cross-linking activity; s-nexilin has one ABD at the middle region and lacks cross-linking activity. s-Nexilin colocalizes with vinculin, talin, and paxillin at cell-matrix adherens junctions and focal contacts. |
Protein purification, in vitro F-actin binding assay, F-actin cross-linking assay, immunofluorescence microscopy |
The Journal of cell biology |
High |
9832551
|
| 2009 |
Nexilin is a Z-disk protein in cardiac and skeletal muscle; loss of nexilin in zebrafish disrupts Z-disk stability and causes heart failure. Expression of disease-associated NEXN mutant alleles in zebrafish induces Z-disk damage in a dominant-negative manner. Increased mechanical strain aggravates Z-disk damage in nexilin-deficient skeletal muscle, indicating nexilin protects Z-disks from mechanical trauma. |
Zebrafish morpholino knockdown, transgenic expression of mutant NEXN alleles, electron microscopy of Z-disk ultrastructure, genetic association study |
Nature medicine |
High |
19881492
|
| 2005 |
NELIN (human nexilin) product associates with F-actin in cells. Stable transfection of NELIN into HeLa cells increases cell migration by ~2-fold and adhesion by ~1.7-fold compared to empty vector controls. |
Immunofluorescence, immunoprecipitation, stable transfection, migration and adhesion assays |
Biochemical and biophysical research communications |
Medium |
15823560
|
| 2010 |
Two HCM-associated NEXN missense mutations (Q131E and R279C) cause local accumulations of nexilin in cells. The Q131E mutation abolishes F-actin binding of the actin-binding domain fragment and decreases binding of full-length NEXN to α-actin as demonstrated by co-immunoprecipitation. |
Cellular transfection, immunofluorescence, co-immunoprecipitation, F-actin binding assay in C2C12 cells |
American journal of human genetics |
Medium |
20970104
|
| 2013 |
Nexilin binds preferentially to IRS1 (over IRS2) in L6 skeletal muscle myotubes under basal conditions, and this complex is disassembled by insulin. Functional silencing of nexilin enhances recruitment of p85α to IRS1, increases PI-3,4,5-P3 formation, and enhances AKT activation and glucose uptake, while nexilin overexpression inhibits IRS1-to-AKT signaling. Disruption of actin with Latrunculin B abolishes the nexilin–IRS1 spatial association. |
Co-immunoprecipitation, siRNA knockdown, nexilin overexpression, PI3K activity assay, AKT phosphorylation immunoblot, glucose uptake assay in L6 myotubes |
PloS one |
Medium |
23383252
|
| 2014 |
NEXN inhibits cardiac differentiation by suppressing GATA4 expression. Cardiac-selective NEXN transgenic mice develop atrial septal defects. Disease-associated NEXN mutations (K199E, L227S) also inhibit GATA4 expression, establishing NEXN as a negative regulator of GATA4-dependent cardiac development. |
Knockdown, overexpression, and rescue experiments in P19cl6 cells; transgenic mouse model; GATA4 expression analysis |
Cardiovascular research |
Medium |
24866383
|
| 2015 |
Constitutive Nexn knockout mice develop rapidly progressive dilated cardiomyopathy with left ventricular dilation, wall thinning, systolic dysfunction, and collagen/elastin deposits (endomyocardial fibroelastosis) by postnatal day 6, establishing an essential role of nexilin in cardiac structure and function. |
Constitutive knockout mouse model, echocardiography, histology, immunostaining |
Basic research in cardiology |
High |
26659360
|
| 2018 |
Nexilin localizes to dense bodies and dense bands in smooth muscle cells (analogous to Z-discs). NEXN expression in SMCs is controlled by actin polymerization state and by transcriptional coactivators MRTF (MYOCD, MKL1, MKL2) and YAP/TAZ. Silencing NEXN reduces actin polymerization, cell migration, and smooth muscle marker expression, indicating a positive feedback loop between nexilin and actin dynamics. |
Immunofluorescence, immunoelectron microscopy, Latrunculin B treatment, NEXN knockdown/overexpression, MRTF/YAP overexpression, promoter assay |
Scientific reports |
Medium |
30158653
|
| 2019 |
NEXN is a component of junctional membrane complexes at cardiac dyads. Loss of Nexn in global and cardiomyocyte-specific knockout mice causes dilated cardiomyopathy. NEXN interacts with junctional sarcoplasmic reticulum proteins, is essential for optimal calcium transients, and is required for initiation and formation of T-tubule invagination. |
Global and cardiomyocyte-specific KO mice, electron microscopy, confocal microscopy, calcium transient measurements, RNA sequencing, mass spectrometry |
Circulation |
High |
30982350
|
| 2019 |
NEXN (nexilin) exerts a protective role against atherosclerosis; NEXN protein inhibits TLR4 oligomerization and downstream NF-κB activity, reducing expression of adhesion molecules and inflammatory cytokines in endothelial cells. The anti-inflammatory/anti-atherosclerotic effects of the lncRNA NEXN-AS1 are abolished by NEXN knockdown, placing NEXN downstream of NEXN-AS1 in this pathway. In ApoE-KO mice, NEXN deficiency promotes atherosclerosis while augmented NEXN expression deters it. |
In vitro knockdown/overexpression, TLR4 oligomerization assay, NF-κB reporter, monocyte adhesion assay, ApoE-KO mouse model with NEXN manipulation |
The Journal of clinical investigation |
Medium |
30589415
|
| 2020 |
Inducible adult cardiomyocyte-specific loss of Nexn in mice causes dilated cardiomyopathy, impairs calcium handling, and leads to a 40% reduction in the transverse tubular component, demonstrating that NEXN is required not only for T-tubule formation during development but also for maintenance of the transverse-axial tubular architecture in adult cardiomyocytes. |
Inducible cardiomyocyte-specific KO mice, confocal microscopy, electron microscopy, calcium transient and myocyte shortening studies, echocardiography |
Circulation. Heart failure |
High |
32635769
|
| 2022 |
CDC-like kinase 4 (CLK4) directly phosphorylates nexilin (NEXN). CLK4 knockdown induces pathological cardiomyocyte hypertrophy, while overexpression of a phosphorylation-mimic NEXN mutant is sufficient to reverse CLK4 knockdown-induced hypertrophy. Restoring NEXN phosphorylation ameliorates myocardial hypertrophy in cardiac-specific Clk4-knockout mice, establishing CLK4 as the kinase writer for NEXN phosphorylation in cardiac hypertrophy regulation. |
Kinase substrate assay, cardiomyocyte-specific Clk4 KO mice, phosphorylation-mimic NEXN mutant overexpression, echocardiography, cardiomyocyte size measurements |
Nature communications |
High |
35907876
|
| 2015 |
NELIN (nexilin) promotes vascular smooth muscle cells (VSMCs) toward a contractile phenotype by activating RhoA, which drives SRF nuclear translocation and SMα-actin expression. NELIN knockdown shifts VSMCs to a synthetic phenotype with decreased RhoA and SRF nuclear localization; the RhoA kinase inhibitor Y-27632 abolishes the NELIN-induced contractile phenotype. |
Lentiviral overexpression and siRNA knockdown in VSMCs, Western blot for RhoA/SRF/SMα-actin, nuclear translocation assay, Rho kinase inhibitor treatment |
Molecular medicine reports |
Medium |
26458985
|
| 2025 |
NEXN interacts with SERCA2 in vascular smooth muscle cells, enhancing SERCA2 SUMOylation, stability, and function. VSMC-specific NEXN knockout exacerbates vascular calcification, while NEXN overexpression alleviates it, operating through the NEXN-SERCA2 interaction and SERCA2 SUMOylation axis. |
VSMC-specific KO and overexpression mouse models, co-immunoprecipitation for NEXN-SERCA2 interaction, SUMOylation assay, multi-transcriptomics analysis |
Nature communications |
High |
40883305
|
| 2025 |
NEXN deficiency in VSMCs promotes phenotypic transition and neointimal hyperplasia through endoplasmic reticulum (ER) stress and Krüppel-like factor 4 (KLF4) signaling. Inhibiting ER stress ameliorates VSMC phenotypic transition and proliferation caused by NEXN deficiency. |
VSMC-specific lineage-tracing mice, NEXN KO, integrative transcriptomics, ER stress inhibitor treatment, cell proliferation and phenotypic marker assays |
JCI insight |
Medium |
40440261
|
| 2025 |
Nexilin binds directly to the C-terminal intracellular loop of GABAA receptor γ-subunits. This interaction regulates cell-surface expression of extrasynaptic γ2-containing GABAA receptors in hippocampal neurons; nexilin upregulation increases surface GABAA receptor numbers and synaptic currents, while the effect requires the actin-binding domain of nexilin (its deletion abolishes the effect). Nexilin also interacts with Rab7b and the lysosomal calcium channel TRPML1, and promotes calcium-dependent fission of late endosomes/lysosomes required for retrograde transport. |
Pulldown, array-based peptide mapping, deep-mutational scanning, siRNA knockdown and overexpression in hippocampal neurons, electrophysiology (GABA-mediated currents), surface GABAA receptor quantification, actin-binding domain deletion mutant |
Neuropharmacology |
Medium |
40812511
|
| 2026 |
Nexilin regulates late endosome/lysosome (LE/Lys) fission and retrograde transport. Depletion of nexilin causes LE/Lys enlargement due to inhibited fission. Nexilin interacts with the small GTPase Rab7b and the lysosomal calcium channel TRPML1; TRPML1 activation rescues LE/Lys enlargement caused by nexilin depletion, indicating nexilin mediates the interaction between LE/Lys and the acto-myosin cytoskeleton for calcium-dependent organelle fission. |
siRNA screen, live imaging of LE/Lys size, Co-immunoprecipitation for Rab7b and TRPML1, TRPML1 agonist rescue experiment, retrograde transport assay |
Cell communication and signaling : CCS |
Medium |
41514273
|
| 2012 |
Nexilin is required for efficient Listeria monocytogenes invasion; siRNA-mediated nexilin knockdown significantly reduces intracellular bacterial levels. Nexilin is a component of L. monocytogenes actin comet tails and EPEC pedestals, accumulating at the distal portion of motile bacterial actin structures. Nexilin knockdown impairs comet tail formation (malformed comet tails) but is dispensable for EPEC pedestal generation. |
siRNA knockdown, immunofluorescence colocalization, bacterial invasion assay (intracellular bacteria quantification), comet tail morphology analysis |
Cellular microbiology |
Medium |
22381134
|
| 2025 |
NEXN overexpression in hepatocellular carcinoma cells reduces β-catenin nuclear accumulation and inhibits EMT. NEXN binds to MYOCD, and together they co-regulate EMT via the WNT/β-catenin signaling pathway. Diminished NEXN expression leads to β-catenin nuclear accumulation and enhanced EMT-driven metastasis. |
Overexpression in HCC cell lines, β-catenin nuclear localization assay, Co-immunoprecipitation for NEXN-MYOCD interaction, in vivo tumor formation, EMT marker Western blot |
iScience |
Low |
41399508
|
| 2024 |
AAV-mediated systemic delivery of Nexn restores cardiac function and extends lifespan in both global Nexn knockout mice and mice carrying the human equivalent G645del mutation, demonstrating that exogenous full-length nexilin can functionally rescue loss-of-function DCM and identifying functional components of nexilin sufficient for this rescue. |
AAV gene delivery (systemic intravenous injection), echocardiography, immunoblot, Nexn global KO and G645del knock-in mouse models |
Genome biology |
Medium |
38783323
|
| 2025 |
NEXN homozygous knockout human iPSC-derived cardiomyocytes show disordered junctional membrane complexes, abnormal excitation-contraction coupling, increased oxidative stress, and decreased energy metabolism, confirming that nexilin is a structural component of junctional membrane complexes essential for excitation-contraction coupling. |
CRISPR/Cas9 knockout in hiPSCs, directed differentiation to cardiomyocytes, electron microscopy, calcium imaging, oxidative stress assays, metabolic assays |
Stem cell research & therapy |
Medium |
40713745
|
| 2024 |
Novel nexilin splice variants exist in mouse and human tissues segregating into myocyte-specific and epithelial-specific isoforms. Heart-specific isoforms differ between atria and ventricles. Different isoforms exhibit distinct self-interaction properties in recombinant protein interaction studies, and critical exons in ABD1 and ABD2 differ between isoforms. |
RT-PCR, tissue expression analysis, recombinant protein interaction studies (pulldown), isoform mapping |
Cells |
Low |
39682766
|