Affinage

PLS3

Plastin-3 · UniProt P13797

Length
630 aa
Mass
70.8 kDa
Annotated
2026-06-10
67 papers in source corpus 25 papers cited in narrative 24 extracted findings
Cross-family judge faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PLS3 encodes T-plastin, a calcium-sensitive actin-bundling protein that cross-links actin filaments and thereby organizes the cytoskeletal architecture underlying cell shape, migration, mechanosensing, and membrane trafficking (PMID:36067297, PMID:7806577). Cryo-EM resolves T-plastin bridging pairs of actin filaments in both parallel and antiparallel orientations through a sequential bundling mechanism in which inter-CHD linkers enable flexible yet stable cross-linking (PMID:36067297). Beyond cross-linking, T-plastin stabilizes individual filaments by displacing cofilin and inhibiting cofilin-mediated depolymerization, and it accelerates Arp2/3-driven actin-based motility—activities retained by an isolated actin-binding domain independent of bundle formation (PMID:15741236). These properties translate into defined cellular roles: T-plastin localizes to the cell cortex and active membrane protrusions where it widens and lengthens F-actin to bridge ECM gaps, and is required for the cortical localization and activation of myosin II (PMID:32968060, PMID:28559444). T-plastin expression is controlled downstream of calcineurin/NFAT signaling, where it drives keratinocyte migration, lamellipodia formation, and FAK/integrin expression (PMID:25226517, PMID:22627769), and its interaction with activated Rab5 promotes endocytosis (PMID:21426900). It binds CORO1C in a calcium-dependent manner to support endocytosis at the neuromuscular junction, an activity that rescues defects in SMN-deficient models (PMID:27499521). In bone, PLS3 localizes to focal adhesions and confers osteoblast responsiveness to ECM stiffness and matrix mineralization, with bundling-defective patient mutants failing to rescue this function (PMID:38089885). Loss-of-function PLS3 variants cause X-linked early-onset osteoporosis with fractures, whereas specific actin-binding-domain missense variants act through a gain-of-function mechanism to cause congenital diaphragmatic hernia and body-wall defects (PMID:37751738, PMID:24088043). PLS3 transcription is repressed by CpG island methylation and by ZNF471-directed recruitment of KAP1 and H3K9me3 deposition at its promoter (PMID:22495182, PMID:25806852, PMID:29610526).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1994 High

    Established that T-plastin is not functionally redundant with its paralog L-plastin but plays distinct, cell-type-specific roles in actin organization, defining the protein as a bona fide actin-organizing factor with unique behavior.

    Evidence Overexpression of both isoforms in CV-1 and LLC-PK1 cells with detergent extraction and imaging

    PMID:7806577

    Open questions at the time
    • Did not resolve the structural basis of isoform-specific filament association
    • Mechanism of microvillar versus stress-fiber selectivity not defined
  2. 1995 High

    Showed that T-plastin actin-bundling activity is functionally required for actin-driven cellular events by demonstrating its necessity for Shigella invasion, linking bundle architecture to a discrete biological outcome.

    Evidence Dominant-negative truncated T-plastin construct, immunofluorescence co-localization, and electron microscopy in HeLa cells

    PMID:7721941

    Open questions at the time
    • The general (non-infection) cellular processes requiring bundling were not addressed
    • Did not separate bundling from filament-stabilization activities
  3. 1999 Medium

    Defined the transcriptional control elements of T-plastin and first linked CpG island methylation to its silencing, opening the question of epigenetic regulation.

    Evidence S1 mapping, promoter/enhancer reporter assays, DNA footprinting, and methylation analysis

    PMID:10025506

    Open questions at the time
    • Trans-acting factors driving methylation not identified
    • Functional consequences of enhancer silencing in disease not established
  4. 2005 High

    Separated T-plastin's filament-stabilizing activity from its cross-linking activity, showing it competes with cofilin and promotes Arp2/3-based motility independent of bundle formation.

    Evidence Biomimetic VCA-bead motility assay, in vitro depolymerization assay, and cell-based expression of an ABD1-only fragment

    PMID:15741236

    Open questions at the time
    • Did not establish whether cofilin competition operates in vivo
    • Quantitative contribution of each activity to migration unresolved
  5. 2011 Medium

    Connected T-plastin to membrane trafficking by identifying its specific interaction with activated Rab5 and its enhancement of endocytosis.

    Evidence Affinity pulldown with constitutively active Rab5, co-localization, and fluid-phase endocytosis assay in Cos-1 cells

    PMID:21426900

    Open questions at the time
    • Direct versus indirect Rab5 binding not distinguished
    • Single cell line, no reciprocal validation
  6. 2012 Medium

    Placed T-plastin downstream of calcium/calcineurin/NFAT signaling and linked its aberrant expression to malignant lymphocyte phenotypes including migration and apoptosis resistance.

    Evidence PMA/ionomycin stimulation, calcineurin inhibitor treatment, and migration/apoptosis assays in Sézary cells; plus pyrosequencing and reporter assays linking promoter hypomethylation to aberrant expression

    PMID:22495182 PMID:22627769 PMID:25806852

    Open questions at the time
    • Direct NFAT binding to the PLS3 promoter not demonstrated
    • Causal link between expression and apoptosis resistance correlative
  7. 2013 Medium

    Identified PLS3 as the causal gene for X-linked osteoporosis with fractures, establishing a Mendelian disease link and an unexpected role in bone.

    Evidence Whole-exome and Sanger sequencing in families plus zebrafish in vivo functional analysis

    PMID:24088043

    Open questions at the time
    • Cellular mechanism in bone not resolved at discovery
    • How an actin-bundler regulates mineralization unknown at the time
  8. 2016 High

    Demonstrated that PLS3 functions in an endocytic pathway via a calcium-dependent interaction with CORO1C, providing a mechanistic basis for its protective effect in motor neuron disease models.

    Evidence Proteomics, biochemical binding assays, FM1-43 endocytosis assays, and in vivo rescue in SMN-deficient zebrafish and mouse models

    PMID:27499521

    Open questions at the time
    • How the PLS3-CORO1C complex couples to the endocytic machinery not defined
    • Relationship between bundling activity and endocytic rescue unresolved
  9. 2017 High

    Defined a cortical role for T-plastin in activating myosin II and organizing the basement membrane, and showed it mediates hypoxia-induced endocytosis independent of the HIF system.

    Evidence In utero siRNA depletion in mouse epidermis with myosin II inhibition; SILAC proteomics with FM1-43/mCLING trafficking assays under hypoxia

    PMID:28218996 PMID:28559444

    Open questions at the time
    • Mechanism by which T-plastin activates myosin II not defined
    • Signal coupling hypoxia to T-plastin membrane recruitment unknown
  10. 2017 Medium

    Identified LCP1 as a calcium-modulated PLS3 partner and showed a patient mutation disrupts both the interaction and intracellular calcium regulation.

    Evidence Co-immunoprecipitation and intracellular Ca2+ measurement with mutation testing

    PMID:28646489

    Open questions at the time
    • Single Co-IP without reciprocal validation
    • Mechanism linking the interaction to Ca2+ handling not defined
  11. 2018 Medium

    Identified ZNF471 as a sequence-specific repressor of PLS3 that recruits KAP1 to deposit H3K9me3, adding a defined chromatin-based layer of transcriptional control.

    Evidence ChIP-PCR, ectopic ZNF471 expression with transcriptional readout, and KAP1 co-immunoprecipitation

    PMID:29610526

    Open questions at the time
    • Physiological contexts in which this repression operates not defined
    • Interplay with CpG methylation not addressed
  12. 2019 Medium

    Showed PLS3 acts as a genetic modifier in neurodegeneration through a direct interaction with CHP1, broadening its partner network beyond actin and endocytic factors.

    Evidence Transgenic PLS3 overexpression in Chp1 mutant mice with histology, immunofluorescence, and Western blot

    PMID:31607845

    Open questions at the time
    • NHE1 membrane-targeting effect was a trend, not statistically established
    • Direct CHP1 binding interface not mapped
  13. 2022 High

    Resolved the structural mechanism of bundling, showing T-plastin cross-links filaments in both parallel and antiparallel orientations through a sequential mechanism dependent on inter-CHD linkers.

    Evidence Cryo-EM with a machine-learning pipeline plus biochemical, cell biological, and mutagenesis validation

    PMID:36067297

    Open questions at the time
    • Calcium-dependent conformational regulation not fully resolved structurally
    • Structural basis of disease mutations not directly mapped in this study
  14. 2023 Medium

    Mechanistically linked PLS3 to bone disease by showing its actin-bundling activity is specifically required for osteoblast mechanosensing of ECM stiffness and matrix mineralization, and that distinct missense variants cause CDH via a gain-of-function mechanism.

    Evidence Stable knockdown in MC3T3-E1 cells with stiffness hydrogels and structure-function mutant rescue; mouse knockin of p.Trp499Cys with phenotype and BMD measurement plus structural modeling

    PMID:37751738 PMID:38089885

    Open questions at the time
    • Gain-of-function biochemical mechanism for CDH variants not directly demonstrated
    • How focal adhesion bundling couples to mineralization signaling unresolved
  15. 2024 Medium

    Established functional compensation among actin-bundlers in vivo and placed PLS3 upstream of Wnt signaling in bone-forming cells.

    Evidence Zebrafish morpholino knockdown with ACTN1/ACTN4/FSCN1 mRNA rescue and RNA-seq in MLO-Y4 osteocyte-like cells

    PMID:39273077

    Open questions at the time
    • Direct mechanism linking PLS3 to Wnt regulation not defined
    • Transcriptomic changes are associations, not validated effectors
  16. 2025 Medium

    Proposed that plastin bundling activity is pH-sensitive, identifying T-plastin as a candidate cytoskeletal pH sensor via the ABD1 actin interface.

    Evidence In vitro pH-dependent F-actin bundling assays and His207 site-directed mutagenesis (preprint, primarily modeled on PLS2)

    PMID:bio_10.1101_2025.03.26.645573

    Open questions at the time
    • Not peer-reviewed; PLS3 pH sensing inferred alongside PLS2 as model
    • Physiological relevance of pH sensing in vivo not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • How calcium and pH binding mechanically gate the bundling/stabilization switch, and how this connects the actin, endocytic, and mechanosensing functions into a unified regulatory logic, remains unresolved.
  • No integrated structural model coupling Ca2+/pH sensing to disease mutations
  • Tissue-specific selection of bundling versus stabilization activity undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 5 GO:0140299 molecular sensor activity 1
Localization
GO:0005856 cytoskeleton 3 GO:0005886 plasma membrane 3 GO:0005768 endosome 1 GO:0005829 cytosol 1
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-1643685 Disease 2
Partners
CHP1CORO1CLCP1RAB5

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2022 Cryo-EM structural analysis revealed that T-plastin bridges pairs of actin filaments in both parallel and antiparallel orientations through a sequential bundling mechanism, populating distinct structural landscapes in each orientation. Inter-CHD linkers were identified as key structural elements enabling flexible but stable cross-linking. Cryo-electron microscopy with machine-learning-enabled pipeline, biochemical assays, cell biological experiments, mutagenesis Proceedings of the National Academy of Sciences of the United States of America High 36067297
1995 T-plastin is functionally required for Shigella flexneri entry into HeLa cells. T-plastin co-localizes with parallel actin filament bundles in parasite-induced cellular protrusions, and expression of a truncated T-plastin lacking one actin-binding site inhibits bacterial entry, demonstrating a direct functional role in actin bundle architecture during invasion. Transfection of truncated T-plastin dominant-negative construct, immunofluorescence co-localization, electron microscopy The Journal of cell biology High 7721941
1994 T-plastin and L-plastin isoforms play distinct, cell-type-specific roles in actin filament organization. In LLC-PK1 epithelial cells, T-plastin induces shape changes in microvilli and remains associated with microvillar actin filaments after detergent extraction, while L-plastin has no effect on microvilli. In CV-1 fibroblast-like cells, overproduction of both isoforms induces cell rounding and reorganization of actin stress fibers, but T-plastin is largely extracted by non-ionic detergent while L-plastin remains associated with microfilaments. Overexpression in CV-1 and LLC-PK1 cell lines, non-ionic detergent extraction, immunofluorescence The Journal of cell biology High 7806577
2005 T-plastin increases the velocity of Arp2/3-mediated actin-based bead movement by ~1.5-fold, stabilizes actin comets, displaces cofilin, and inhibits cofilin-mediated actin filament depolymerization in vitro. A bundling-incompetent variant comprising only ABD1 had similar stabilizing effects, indicating that T-plastin controls actin turnover via filament binding independently of cross-link/bundle formation. Quantitative biomimetic motility assay (VCA-coated beads in cell-free extracts), in vitro depolymerization assay, cell-based overexpression of ABD1 fragment Journal of cell science High 15741236
2016 PLS3 overexpression restores endocytosis in SMN-deficient cells and neuromuscular junctions. CORO1C was identified as a direct binding partner of PLS3, with their interaction being calcium-dependent. Both PLS3 and CORO1C overexpression elevate F-actin levels and rescue endocytosis defects and axonal truncation in Smn-depleted zebrafish, placing PLS3 in an endocytic pathway downstream of SMN. Proteomics, biochemical interaction assays, FM1-43 endocytosis assay in NMJs, SMN-knockdown zebrafish rescue experiments, PLS3 overexpression in SMA mouse model American journal of human genetics High 27499521
2020 T-plastin promotes membrane protrusions and enables cells to bridge ECM gaps during migration. T-plastin is specifically enriched in active protrusions where F-actin is devoid of non-muscle myosin II activity, and it widens and lengthens protrusions to stabilize actin filaments. Micropatterned ECM substrates, live-cell imaging, T-plastin knockdown/knockout, co-localization with myosin II markers Nature communications High 32968060
2017 T-plastin (Pls3) localizes to the cell cortex and is essential for the localization and activation of myosin II in mouse epidermal cells. In utero depletion of Pls3 caused basement membrane and polarity defects in the epidermis; apicobasal polarity defects were secondary to basement membrane disruption. Inhibition of myosin II motor activity similarly disrupted basement membrane organization. In utero siRNA depletion in mouse embryos, immunofluorescence, myosin II inhibition Science signaling High 28559444
2011 T-plastin (and L-plastin) interacts specifically with activated (GTP-bound) Rab5, co-localizes with Rab5 on the plasma membrane and endosomes, and overexpression of T-plastin increases Rab5 activity and the rate of fluid-phase endocytosis in Cos-1 cells. Affinity column pulldown with constitutively active Rab5, co-localization by fluorescence microscopy, fluid-phase endocytosis assay, overexpression Biochemical and biophysical research communications Medium 21426900
2017 T-plastin expression is regulated downstream of the calcineurin/NFAT signaling pathway in keratinocytes. Knockdown of NFAT2 or T-plastin, or treatment with calcineurin inhibitor FK506, reduces T-plastin expression and impairs keratinocyte migration, lamellipodia formation, and FAK and β6-integrin expression. siRNA knockdown, FK506 treatment, scratch and Boyden migration assays, immunofluorescence PloS one Medium 25226517
2012 T-plastin synthesis in Sézary cells and normal lymphocytes can be induced by calcium influx (PMA/ionomycin stimulation), and this induction is suppressed by calcineurin inhibitors and involves the NFAT transcription pathway. Constitutive T-plastin expression in SS cells is associated with resistance to etoposide-induced apoptosis and cell migration toward chemokines TARC/CCL17 and IP-10. PMA/ionomycin stimulation, calcineurin inhibitor treatment, functional migration and apoptosis assays Blood Medium 22627769
2017 T-plastin (PLS3) mediates hypoxia-induced membrane trafficking. T-plastin is recruited to the plasma membrane under hypoxic conditions (identified by SILAC), and T-plastin knockdown cells fail to show the hypoxia-induced increase in membrane endocytosis; this effect is independent of the HIF system. SILAC proteomics, FM1-43 and mCLING membrane trafficking assays, T-plastin knockdown, electron microscopy Acta physiologica (Oxford, England) Medium 28218996
2017 LCP1 (lymphocyte cytosolic protein 1) was identified as a binding partner of PLS3. The p.Ala253_Leu254insAsn mutation in PLS3 disrupts the PLS3–LCP1 interaction. Both PLS3 and LCP1 regulate intracellular Ca2+, and the mutation weakens this regulation. The PLS3–LCP1 interaction is enhanced under low extracellular Ca2+ concentrations. Co-immunoprecipitation (binding partner identification and mutation effect), intracellular Ca2+ measurement Clinical genetics Medium 28646489
2023 PLS3 localizes to focal adhesions in osteoblasts and is required for mechanosensitive responses to ECM stiffness. Depletion of PLS3 does not affect collagen matrix deposition but severely impairs subsequent matrix mineralization. PLS3-depleted osteoblasts are unresponsive to changes in ECM stiffness (no change in cell size, FA length, or FA number on soft vs. stiff substrates). Rescue with wild-type PLS3 but not with three patient-derived actin-bundling-defective mutants restores mechanoresponsiveness, demonstrating that actin-bundling activity is specifically required. Stable PLS3 knockdown in MC3T3-E1 cells, osteogenic differentiation assay, hydrogels of defined stiffness, rescue with wild-type vs. mutant PLS3, focal adhesion quantification Frontiers in cell and developmental biology High 38089885
2019 PLS3 overexpression delays the ataxic phenotype in Chp1 mutant (vacillator) mice, ameliorates axon hypertrophy and axonal swellings in Purkinje neurons, and shows a trend toward increased membrane targeting/expression of NHE1 (an important CHP1 binding partner) in the cerebellum. PLS3 directly interacts with CHP1 (calcineurin-like EF-hand protein 1). Transgenic PLS3 overexpression in Chp1 mutant mice, histological analysis, immunofluorescence, Western blot Frontiers in neuroscience Medium 31607845
1999 The human T-plastin gene promoter contains a CCAAT box, Sp1 motif, and four AP2 motifs but no TATA or Inr sequence. A T-plastin-specific enhancer was identified ~500 bp from the basal promoter consisting of two inverted symmetric octamers. CpG island methylation within the first intron correlates with silencing in leukocyte cells. In leukemia cells, the T-plastin enhancer (but not the SV40 enhancer) fails to activate transcription. S1 mapping, promoter reporter assays (luciferase/CAT), DNA footprinting, restriction enzyme methylation analysis DNA and cell biology Medium 10025506
2012 Promoter hypomethylation of CpG dinucleotides 95-99 within the PLS3 CpG island is specifically associated with aberrant PLS3 expression in Sézary syndrome T cells. In vitro methylation of the cloned PLS3 promoter suppresses transcriptional activity, and 5-azacytidine treatment induces PLS3 expression in PLS3-negative cells. Pyrosequencing of CpG dinucleotides, luciferase reporter assay with methylated promoter construct, 5-azacytidine treatment The Journal of investigative dermatology Medium 22495182 25806852
2023 Specific missense variants in the actin-binding domains of PLS3 (e.g., p.Trp499Cys) cause congenital diaphragmatic hernia and body-wall defects, in contrast to loss-of-function variants that cause osteoporosis. A mouse knockin of c.1497G>C (p.Trp499Cys) recapitulates diaphragm and abdominal-wall defects and shows increased (not decreased) bone mineral density, suggesting these CDH-associated missense variants have a gain-of-function effect on the actin-binding domains. Mouse knockin model, in silico protein structural modeling, clinical exome/genome sequencing with segregation analysis American journal of human genetics Medium 37751738
2013 Pathogenic variants in PLS3 cause X-linked osteoporosis with fractures. In vivo analyses in zebrafish support bone-regulatory properties of PLS3. Whole-exome sequencing, Sanger sequencing, zebrafish in vivo morpholino/genetic analysis The New England journal of medicine Medium 24088043
2024 ACTN1 and ACTN4 (but not FSCN1) can rescue skeletal deformities in zebrafish after pls3 morpholino knockdown, indicating functional compensation among actin-bundling proteins. RNA-seq in Pls3-knockdown MLO-Y4 osteocyte-like cells revealed differential expression of Wnt1, Nos1ap, and Myh3, implicating Wnt and Th17 cell differentiation pathways. WNT2 was significantly increased in patient osteoblast-like cells compared with healthy donors. Zebrafish morpholino knockdown with mRNA rescue, RNA-seq in MLO-Y4 cells, primary fibroblast osteogenic differentiation Cells Medium 39273077
2025 PLS3 (plastin 3) exhibits reduced F-actin bundling activity at alkaline physiological pH, functioning as a cytoskeletal pH sensor. The reduced bundling at elevated pH is linked to decreased affinity of the N-terminal actin-binding domain (ABD1) for actin. A conserved histidine residue (His207 in PLS2 as the model) was identified as one pH-sensing residue; mutation to Lys enhances and mutation to Tyr reduces bundling, modulating pH sensitivity. In vitro F-actin bundling assays at different pH, fibroblast cell experiments with ectopic PLS2/PLS3 expression and pH manipulation, site-directed mutagenesis of His207 bioRxivpreprint Medium bio_10.1101_2025.03.26.645573
1996 T-plastin expression is elevated ~12-fold in cisplatin-resistant T24/DDP10 bladder cancer cells compared to parental cells. Transfection of cisplatin-resistant cells with antisense T-plastin RNA reduced T-plastin expression and increased cisplatin sensitivity, indicating T-plastin contributes to cisplatin resistance. mRNA differential display, Northern blot, antisense RNA transfection with drug sensitivity assay FEBS letters Medium 8941723
2015 T-plastin was identified as a novel host cell response factor regulating HCV replication. Chemical proteomic profiling in HCV-infected cells identified T-plastin as differentially labeled by thiol-reactive probes, and its regulation was associated with HCV replication. Transcriptome analysis combined with quantitative chemical proteomic profiling using thiol-reactive probes (activity-based protein profiling) Scientific reports Low 25909246
2018 Bioinformatic analysis of all reported PLS3 disease mutations identified a critical LOOP-1 region (residues ~240-266) that physically connects the CH1 and CH2 domains of ABD1 and is located at the ABD1-ABD2 interface, predicting it to be crucial for conformational transitions and actin-binding function of plastin-3. Homology modelling, molecular dynamics simulation, targeted gene sequencing International journal of endocrinology Low 30405713
2009 ZNF471 directly binds to the promoter of PLS3 (and TFAP2A) and transcriptionally represses PLS3 expression by recruiting co-repressor KAP1, leading to H3K9me3 enrichment at the PLS3 promoter. ChIP-PCR, ectopic ZNF471 expression with transcriptional readout, co-immunoprecipitation of KAP1 Oncogene Medium 29610526

Source papers

Stage 0 corpus · 67 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 PLS3 mutations in X-linked osteoporosis with fractures. The New England journal of medicine 161 24088043
1995 Cytoskeletal rearrangements and the functional role of T-plastin during entry of Shigella flexneri into HeLa cells. The Journal of cell biology 139 7721941
2016 The Power of Human Protective Modifiers: PLS3 and CORO1C Unravel Impaired Endocytosis in Spinal Muscular Atrophy and Rescue SMA Phenotype. American journal of human genetics 133 27499521
1994 Functional differences between L- and T-plastin isoforms. The Journal of cell biology 83 7806577
2014 Osteoporosis caused by mutations in PLS3: clinical and bone tissue characteristics. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 73 24616189
2005 Actin-filament cross-linking protein T-plastin increases Arp2/3-mediated actin-based movement. Journal of cell science 71 15741236
2015 A novel splice mutation in PLS3 causes X-linked early onset low-turnover osteoporosis. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 65 25209159
2003 Aberrant expression of T-plastin in Sezary cells. Cancer research 63 14612505
2018 Zinc-finger protein 471 suppresses gastric cancer through transcriptionally repressing downstream oncogenic PLS3 and TFAP2A. Oncogene 48 29610526
1996 Increased expression of T-plastin gene in cisplatin-resistant human cancer cells: identification by mRNA differential display. FEBS letters 46 8941723
1998 Search for genes involved in UV-resistance in human cells by mRNA differential display: increased transcriptional expression of nucleophosmin and T-plastin genes in association with the resistance. Biochemical and biophysical research communications 43 9703972
2017 PLS3 Deletions Lead to Severe Spinal Osteoporosis and Disturbed Bone Matrix Mineralization. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 42 28777485
2017 PLS3 sequencing in childhood-onset primary osteoporosis identifies two novel disease-causing variants. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 40 28748388
2008 Expression of T-plastin, FoxP3 and other tumor-associated markers by leukemic T-cells of cutaneous T-cell lymphoma. Leukemia & lymphoma 39 18569641
2012 The mouse DXZ4 homolog retains Ctcf binding and proximity to Pls3 despite substantial organizational differences compared to the primate macrosatellite. Genome biology 37 22906166
2013 Correlation of PLS3 expression with disease severity in children with spinal muscular atrophy. Journal of human genetics 34 24172247
2022 Structural mechanism for bidirectional actin cross-linking by T-plastin. Proceedings of the National Academy of Sciences of the United States of America 31 36067297
2015 Promoter-Specific Hypomethylation Is Associated with Overexpression of PLS3, GATA6, and TWIST1 in the Sezary Syndrome. The Journal of investigative dermatology 31 25806852
2011 Interaction of activated Rab5 with actin-bundling proteins, L- and T-plastin and its relevance to endocytic functions in mammalian cells. Biochemical and biophysical research communications 30 21426900
2017 PLS3 Mutations in X-Linked Osteoporosis: Clinical and Bone Characteristics of Two Novel Mutations. Hormone research in paediatrics 28 28605746
2020 T-Plastin reinforces membrane protrusions to bridge matrix gaps during cell migration. Nature communications 27 32968060
2017 Teriparatide Treatment in Patients With WNT1 or PLS3 Mutation-Related Early-Onset Osteoporosis: A Pilot Study. The Journal of clinical endocrinology and metabolism 27 27732335
2012 Inducible expression and pathophysiologic functions of T-plastin in cutaneous T-cell lymphoma. Blood 27 22627769
2020 Biomarkers in WNT1 and PLS3 Osteoporosis: Altered Concentrations of DKK1 and FGF23. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 26 31968132
2017 T-plastin is essential for basement membrane assembly and epidermal morphogenesis. Science signaling 26 28559444
2012 Regulation of T-plastin expression by promoter hypomethylation in primary cutaneous T-cell lymphoma. The Journal of investigative dermatology 26 22495182
2017 A novel large fragment deletion in PLS3 causes rare X-linked early-onset osteoporosis and response to zoledronic acid. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 25 28620780
2018 A novel frameshift deletion in PLS3 causing severe primary osteoporosis. Journal of human genetics 22 29884797
2016 Atypical femur fracture in an adolescent boy treated with bisphosphonates for X-linked osteoporosis based on PLS3 mutation. Bone 22 27477003
1999 Differential regulation of human T-plastin gene in leukocytes and non-leukocytes: identification of the promoter, enhancer, and CpG island. DNA and cell biology 21 10025506
2019 NOVEL MUTATIONS IN THE WNT1, TMEM38B, P4HB, AND PLS3 GENES IN FOUR UNRELATED CHINESE FAMILIES WITH OSTEOGENESIS IMPERFECTA. Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists 20 30913006
2020 Unique, Gender-Dependent Serum microRNA Profile in PLS3 Gene-Related Osteoporosis. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 19 32453450
2017 Hypoxia-stimulated membrane trafficking requires T-plastin. Acta physiologica (Oxford, England) 18 28218996
2014 T-plastin expression downstream to the calcineurin/NFAT pathway is involved in keratinocyte migration. PloS one 18 25226517
2020 PLS3 Mutations Cause Severe Age and Sex-Related Spinal Pathology. Frontiers in endocrinology 16 32655496
2021 Bone material properties and response to teriparatide in osteoporosis due to WNT1 and PLS3 mutations. Bone 15 33618074
2019 A novel nonsense variant in PLS3 causes X-linked osteoporosis in a Chinese family. Annals of human genetics 14 31347706
2019 Analysis of FUS, PFN2, TDP-43, and PLS3 as potential disease severity modifiers in spinal muscular atrophy. Neurology. Genetics 14 32042914
2018 Clinical, Genetics, and Bioinformatic Characterization of Mutations Affecting an Essential Region of PLS3 in Patients with BMND18. International journal of endocrinology 14 30405713
2020 A novel mutation in PLS3 causes extremely rare X-linked osteogenesis imperfecta. Molecular genetics & genomic medicine 13 33166085
2017 Functional analysis of p.Ala253_Leu254insAsn mutation in PLS3 responsible for X-linked osteoporosis. Clinical genetics 13 28646489
2021 X-Linked Osteogenesis Imperfecta Possibly Caused by a Novel Variant in PLS3. Genes 12 34946798
2015 Expression of the PLS3 Gene in Circulating Cells in Patients with Colorectal Cancer. Polski przeglad chirurgiczny 11 26146096
2013 A common gene variant in PLS3 predicts colon cancer recurrence in women. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 11 23549633
2022 Identification of a novel splicing mutation and genotype-phenotype correlations in rare PLS3-related childhood-onset osteoporosis. Orphanet journal of rare diseases 10 35752817
2019 Genetic variants in the PLS3 gene are associated with osteoporotic fractures in postmenopausal Chinese women. Acta pharmacologica Sinica 9 30837644
2015 Chemical proteomic identification of T-plastin as a novel host cell response factor in HCV infection. Scientific reports 9 25909246
2023 Impaired bone strength and bone microstructure in a novel early-onset osteoporotic rat model with a clinically relevant PLS3 mutation. eLife 7 37083757
2023 The intricate mechanism of PLS3 in bone homeostasis and disease. Frontiers in endocrinology 7 37484945
2023 PLS3 missense variants affecting the actin-binding domains cause X-linked congenital diaphragmatic hernia and body-wall defects. American journal of human genetics 7 37751738
2023 PLS3 Mutations in X-Linked Osteoporosis: Clinical and Genetic Features in Five New Families. Calcified tissue international 7 38043102
2003 Changes in T-plastin expression with human trophoblast differentiation. Reproductive biomedicine online 7 14567899
2019 PLS3 Overexpression Delays Ataxia in Chp1 Mutant Mice. Frontiers in neuroscience 6 31607845
2025 Bone microarchitecture and strength in men and women with PLS3 gene variants assessed with HR-pQCT. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 5 39658012
2006 Generation and characterization of monoclonal antibodies that specifically recognize p65/L-plastin isoform but not T-plastin isoform. Bioscience, biotechnology, and biochemistry 5 16794320
2024 T-plastin contributes to epithelial-mesenchymal transition in human lung cancer cells through FAK/AKT/Slug axis signaling pathway. BMB reports 4 38835117
2023 PLS3 promotes papillary thyroid carcinoma progression by activating the Notch signaling pathway. Environmental toxicology 4 37347555
2024 Functional Insights in PLS3-Mediated Osteogenic Regulation. Cells 3 39273077
2024 Early-Onset Osteoporosis: Molecular Analysis in Large Cohort and Focus on the PLS3 Gene. Calcified tissue international 3 39316135
2023 The actin-bundling protein, PLS3, is part of the mechanoresponsive machinery that regulates osteoblast mineralization. Frontiers in cell and developmental biology 3 38089885
2022 Lipocalin-2 is associated with FGF23 in WNT1 and PLS3 osteoporosis. Frontiers in endocrinology 3 36157448
2026 PLS3-AS1 promotes colorectal cancer progression and radioresistance by sustaining NF-κB signaling. Biochemical and biophysical research communications 0 41662797
2026 Multigated DNA Cascade Amplifier for Ultrasensitive Spatiotemporal Imaging of PLS3 mRNA at the Single-Cell Level for Early Detection of Breast Cancer Metastasis. Analytical chemistry 0 41961955
2025 X-linked Osteoporosis due to PLS3 Pathogenic Variant: Case Report on Zoledronic Acid Treatment in Siblings. Journal of clinical research in pediatric endocrinology 0 40959584
2025 Targeted Gene Sequencing in a Male Adult Diagnosed With X-Linked Osteoporosis Due to a Novel p.(Arg398Profs*2) PLS3 Variant. JCEM case reports 0 41018172
2024 Correction: Osteoporotic Burst Fracture in a Young Male Adult as First Presentation of a Rare PLS3 Mutation: A Case Report. Cureus 0 38347973
2023 Osteoporotic Burst Fracture in a Young Male Adult as First Presentation of a Rare PLS3 Mutation: A Case Report. Cureus 0 38283430

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