Affinage

PLS3

Plastin-3 · UniProt P13797

Length
630 aa
Mass
70.8 kDa
Annotated
2026-04-28
67 papers in source corpus 23 papers cited in narrative 23 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PLS3 (T-plastin) is a calcium- and pH-sensitive actin-bundling protein that cross-links actin filaments in both parallel and antiparallel orientations via tandem calponin-homology domains connected by flexible inter-CHD linkers, stabilizing actin-based protrusions, regulating endocytosis, and transducing mechanical signals in diverse cell types (PMID:36067297, PMID:7721941, PMID:32968060, PMID:38089885). Beyond bundling, PLS3 inhibits cofilin-mediated actin depolymerization independently of its cross-linking activity, interacts with activated Rab5 and the calcium-dependent binding partner CORO1C to promote endocytic membrane trafficking, and controls cortical myosin II activation required for basement membrane assembly (PMID:15741236, PMID:21426900, PMID:27499521, PMID:28559444). PLS3 expression is governed by CpG island methylation status and can be induced through the calcineurin/NFAT signaling pathway or repressed by the ZNF471/KAP1 complex via H3K9 trimethylation at its promoter (PMID:25806852, PMID:22627769, PMID:29610526). Loss-of-function PLS3 variants cause X-linked osteoporosis by impairing mechanosensitive osteoblast mineralization, whereas gain-of-function missense variants affecting actin-binding domains cause congenital diaphragmatic hernia with increased bone mineral density (PMID:38089885, PMID:37751738).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1994 High

    Establishing that T-plastin and L-plastin are functionally distinct isoforms: T-plastin uniquely associates with microvillar actin filaments and reorganizes actin architecture in a cell-type-specific manner, defining it as a non-hematopoietic actin-bundling protein.

    Evidence Overexpression in epithelial and fibroblast cell lines with detergent extraction fractionation and morphological analysis

    PMID:7806577

    Open questions at the time
    • Structural basis for isoform-specific actin interactions not determined
    • In vivo physiological relevance not tested
  2. 1995 High

    Demonstrating that T-plastin's actin-bundling activity is functionally required for actin-dependent cellular processes: T-plastin localizes to bacterium-induced actin protrusions and a dominant-negative truncation blocks Shigella invasion, establishing it as an essential organizer of actin protrusions.

    Evidence Dominant-negative T-plastin truncation, immunofluorescence, and electron microscopy in Shigella-infected HeLa cells

    PMID:7721941

    Open questions at the time
    • Whether bundling versus filament stabilization is the critical activity was unresolved
    • No genetic loss-of-function model tested
  3. 1999 High

    Resolving how T-plastin expression is restricted to non-hematopoietic cells: CpG island methylation silences the T-plastin promoter in leukocytes, and a tissue-specific enhancer is inactive in those cells.

    Evidence S1 mapping, promoter/enhancer reporter assays, restriction-enzyme methylation analysis, and DNA footprinting of the PLS3 promoter

    PMID:10025506

    Open questions at the time
    • Trans-acting factors responsible for methylation not identified
    • In vivo chromatin context not examined
  4. 2005 High

    Separating actin-bundling from filament-stabilizing functions: T-plastin increases Arp2/3-based actin motility speed and displaces cofilin even without cross-linking, establishing a bundling-independent role in controlling actin turnover dynamics.

    Evidence Biomimetic VCA-bead motility assay in cell-free extracts with bundling-incompetent ABD1 mutant, in vitro depolymerization assay

    PMID:15741236

    Open questions at the time
    • Molecular mechanism of cofilin displacement not structurally resolved
    • Relative contributions of bundling vs. stabilization in vivo remain unclear
  5. 2011 Medium

    Linking T-plastin to endocytic machinery: T-plastin binds activated (GTP-bound) Rab5 and enhances fluid-phase endocytosis, connecting actin bundling to vesicular trafficking.

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

    PMID:21426900

    Open questions at the time
    • Reciprocal validation of binding in endogenous context lacking
    • Structural basis of PLS3–Rab5 interaction not determined
    • Whether Rab5 interaction requires bundling competence unknown
  6. 2012 Medium

    Placing PLS3 expression under calcineurin/NFAT transcriptional control and linking it to disease-relevant cell behaviors: calcium/NFAT signaling induces T-plastin expression, which confers apoptosis resistance and promotes chemokine-directed migration in Sézary syndrome cells; promoter hypomethylation underlies aberrant expression in these malignant T cells.

    Evidence Pharmacological calcineurin inhibition, PMA/ionomycin stimulation, apoptosis and migration assays; pyrosequencing of CpG dinucleotides in Sézary cells

    PMID:22495182 PMID:22627769

    Open questions at the time
    • Whether NFAT binds the PLS3 promoter directly was not shown by ChIP
    • Causality between methylation and NFAT-driven induction not dissected
  7. 2015 High

    Providing direct mechanistic proof that promoter methylation controls PLS3 transcription: in vitro methylation of the cloned PLS3 promoter silences reporter expression, and pharmacological demethylation reactivates PLS3 in PLS3-negative T cells.

    Evidence In vitro promoter methylation with luciferase reporter, 5-azacytidine treatment of Jurkat cells

    PMID:25806852

    Open questions at the time
    • Specific CpG sites critical for silencing not individually mutated
    • In vivo relevance of demethylation in normal T-cell biology unclear
  8. 2016 High

    Connecting PLS3 to endocytic rescue in spinal muscular atrophy: PLS3 overexpression restores impaired endocytosis in SMN-deficient cells via a pathway involving its calcium-dependent binding partner CORO1C, establishing a molecular mechanism for PLS3 as an SMA disease modifier.

    Evidence Proteomics, calcium-dependent Co-IP, fluid-phase endocytosis assay, FM1-43 presynaptic uptake in SMA mouse NMJs, zebrafish rescue

    PMID:27499521

    Open questions at the time
    • Stoichiometry and structural basis of PLS3–CORO1C complex not resolved
    • Whether endocytic rescue is sufficient for motor neuron survival in vivo not demonstrated
  9. 2017 High

    Revealing a cortical signaling role for PLS3 beyond bundling: PLS3 is required for cortical myosin II localization and activation, and loss of PLS3 disrupts basement membrane assembly and secondary epithelial polarity in mouse epidermis.

    Evidence In utero siRNA depletion in mouse embryonic skin, live imaging, myosin II inhibitor epistasis

    PMID:28559444

    Open questions at the time
    • How PLS3 recruits or activates myosin II at the cortex is unknown
    • Whether this role generalizes beyond epidermal epithelium untested
  10. 2017 Medium

    Identifying PLS3 as a hypoxia-responsive regulator of membrane trafficking independent of HIF: PLS3 is recruited to the plasma membrane under hypoxia and its depletion abolishes hypoxia-induced endocytosis.

    Evidence SILAC proteomics, PLS3 knockdown, FM1-43/mCLING membrane trafficking assays, electron microscopy

    PMID:28218996

    Open questions at the time
    • Signal linking hypoxia to PLS3 membrane recruitment not identified
    • Independence from HIF not validated by HIF knockout
  11. 2018 Medium

    Identifying ZNF471/KAP1 as a direct transcriptional repressor of PLS3 through H3K9me3 deposition, providing a chromatin-level mechanism for PLS3 silencing complementary to DNA methylation.

    Evidence ChIP-PCR for ZNF471 and H3K9me3 at PLS3 promoter, ectopic ZNF471 expression, Co-IP for KAP1

    PMID:29610526

    Open questions at the time
    • Relationship between ZNF471-mediated repression and CpG methylation not tested
    • Physiological contexts where ZNF471 controls PLS3 unclear
  12. 2020 High

    Defining PLS3's role in cell migration mechanics: PLS3 stabilizes and extends membrane protrusions specifically across ECM gaps where myosin II is excluded, establishing it as a protrusion-promoting factor in discontinuous ECM environments.

    Evidence Micropatterned ECM substrates, TIRF/confocal live imaging, PLS3 knockdown with protrusion metrics

    PMID:32968060

    Open questions at the time
    • Mechanism of mutual exclusion between PLS3 and myosin II not resolved
    • Whether this function extends to 3D migration contexts unknown
  13. 2022 High

    Resolving the structural basis of actin bundling at atomic resolution: cryo-EM revealed that PLS3 uses a sequential binding mechanism through two actin-binding domains with flexible inter-CHD linkers to bridge filament pairs in both parallel and antiparallel orientations.

    Evidence Cryo-EM structure of human PLS3 bound to F-actin, inter-CHD linker mutagenesis, biochemical and cell biological validation

    PMID:36067297

    Open questions at the time
    • Structure of full-length PLS3 in complex with two filaments not obtained
    • How calcium binding to EF-hands modulates the structural mechanism not visualized
  14. 2023 High

    Establishing genotype-phenotype relationships: loss-of-function PLS3 variants cause X-linked osteoporosis by impairing mechanosensitive osteoblast mineralization, while gain-of-function actin-binding domain variants cause congenital diaphragmatic hernia with increased bone density, demonstrating that distinct variant classes produce opposite functional consequences.

    Evidence PLS3-depleted osteoblast rescue with WT/mutant PLS3 on stiffness substrates; mouse knockin of p.Trp499Cys recapitulating CDH and elevated BMD

    PMID:37751738 PMID:38089885

    Open questions at the time
    • Biochemical mechanism underlying gain-of-function bundling not characterized
    • How mechanotransduction defect leads specifically to osteoporosis in patients unknown
  15. 2024 Medium

    Extending functional redundancy analysis: ACTN1 and ACTN4 rescue skeletal defects in PLS3-deficient zebrafish but FSCN1 cannot, and PLS3 loss in osteocytes alters Wnt pathway gene expression, linking PLS3 to osteogenic signaling.

    Evidence Zebrafish morpholino rescue with actin bundlers, RNA-seq in PLS3-knockdown osteocyte-like cells

    PMID:39273077

    Open questions at the time
    • Direct molecular basis for functional redundancy with actinins not determined
    • Wnt pathway changes not validated at protein level or in vivo

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include: how calcium binding to PLS3's EF-hand domains structurally regulates its bundling activity, whether pH sensing via conserved histidine residues operates in vivo to tune PLS3 function, the molecular mechanism by which PLS3 controls cortical myosin II activation, and how gain-of-function actin-binding domain mutations produce diaphragmatic hernia.
  • No high-resolution structure of calcium-bound or pH-modulated PLS3
  • Mechanism linking PLS3 to myosin II cortical recruitment unknown
  • Gain-of-function bundling biochemistry not characterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 6 GO:0005198 structural molecule activity 3
Localization
GO:0005856 cytoskeleton 7 GO:0005886 plasma membrane 3 GO:0005829 cytosol 2 GO:0005768 endosome 1
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-1474244 Extracellular matrix organization 2 R-HSA-1500931 Cell-Cell communication 2
Partners
ACTN1ACTN4CORO1CLCP1RAB5AZNF471

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2022 Cryo-EM structure of human T-plastin (PLS3) bound to actin filaments revealed a sequential bundling mechanism enabling T-plastin to bridge pairs of actin filaments in both parallel and antiparallel orientations, with distinct structural landscapes in each orientation. Inter-CHD linkers were identified as key structural elements underlying flexible but stable cross-linking. Cryo-electron microscopy with machine-learning-enabled pipeline, biochemical assays, cell biological validation, active-site/inter-CHD linker 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; it localizes to bacterium-induced actin protrusions and a truncated T-plastin lacking one actin-binding domain acts as a dominant negative, blocking invasion. T-plastin bundles actin filaments in parallel orientation within cellular protrusions at entry zones. Transfection of truncated dominant-negative T-plastin, immunofluorescence colocalization, electron microscopy of actin ultrastructure The Journal of cell biology High 7721941
1994 T-plastin and L-plastin isoforms have different functional roles in actin filament organization in a cell-type-specific manner: T-plastin associates with microvillar actin filaments after detergent extraction and induces shape changes in microvilli, whereas L-plastin does not affect microvilli and is fully extracted. Overproduction of either isoform reorganizes actin stress fibers into geodesic structures. Overexpression in CV-1 and LLC-PK1 cell lines, detergent extraction fractionation, morphological analysis The Journal of cell biology High 7806577
2005 T-plastin/T-fimbrin increases the velocity of Arp2/3-mediated actin-based bead motility 1.5-fold, stabilizes actin comets, displaces cofilin, and inhibits cofilin-mediated actin depolymerization in vitro. A bundling-incompetent ABD1 variant retains these effects, indicating that T-plastin controls actin turnover through filament binding independently of cross-linking. In cells, ABD1 induces long actin cables. Biomimetic VCA-bead motility assay in cell-free extracts, in vitro F-actin depolymerization assay, cell-based overexpression with mutant ABD1 Journal of cell science High 15741236
2016 PLS3 overexpression rescues impaired endocytosis in SMN-deficient cells and restores FM1-43 endocytotic uptake at neuromuscular junction presynaptic terminals in SMA mice. CORO1C was identified as a direct calcium-dependent binding partner of PLS3, and CORO1C overexpression similarly restores fluid-phase endocytosis and rescues axonal defects in SMN-depleted zebrafish by elevating F-actin levels. Proteomics, Co-IP/biochemical binding assay (calcium-dependent), fluid-phase endocytosis assay, FM1-43 presynaptic uptake, SMA mouse rescue experiments, zebrafish knockdown American journal of human genetics High 27499521
2017 T-plastin (Pls3) localizes to the cell cortex in mouse epidermal cells and is essential for basement membrane assembly and epidermal morphogenesis. Loss of Pls3 by in utero depletion causes basement membrane and polarity defects; apicobasal polarity defects are secondary to basement membrane disruption. Pls3 is required for proper localization and activation of myosin II at the cortex, and inhibition of myosin II motor activity disrupts basement membrane organization. In utero siRNA depletion (mouse embryo), live imaging/immunofluorescence localization, myosin II pharmacological inhibition, epistasis analysis of polarity vs. basement membrane defects Science signaling High 28559444
2020 T-Plastin promotes membrane protrusions across ECM gaps during cell migration by stabilizing actin filaments; it widens and lengthens protrusions and is specifically enriched in active protrusions devoid of non-muscle myosin II. Micropatterned ECM experiments show T-Plastin is essential for bridging micron-scale ECM gaps. Micropatterned ECM substrates, TIRF and confocal live imaging, KD with specific protrusion and migration readouts Nature communications High 32968060
2011 Both L- and T-plastin interact specifically with activated (GTP-bound) Rab5 and co-localize with Rab5 on the plasma membrane and endosomes. Overexpression of L- or T-plastin increases Rab5 activity and the rate of fluid-phase endocytosis, indicating plastin-Rab5 interaction promotes endocytic activity. Affinity column pulldown with constitutively active Rab5, co-localization by immunofluorescence, fluid-phase endocytosis assay, overexpression in Cos-1 cells Biochemical and biophysical research communications Medium 21426900
2017 T-plastin expression is regulated downstream of the calcineurin/NFAT pathway in keratinocytes. siRNA knockdown of T-plastin decreases keratinocyte migration, actin lamellipodia formation, and FAK and β6-integrin expression, placing T-plastin as a downstream effector of calcineurin/NFAT-dependent migration. siRNA knockdown, scratch and Boyden migration assays, calcineurin inhibitor (FK506) treatment, siNFAT2, immunofluorescence PloS one Medium 25226517
2017 T-plastin is recruited to the plasma membrane during hypoxia and mediates hypoxia-induced membrane trafficking independently of the HIF system. Knockdown of T-plastin abolishes the increase in membrane endocytosis observed under hypoxic conditions, associated with increased cortical actin density. SILAC proteomics screen, T-plastin knockdown, FM1-43/mCLING membrane trafficking assays, electron microscopy of actin density Acta physiologica Medium 28218996
2017 Mutation p.Ala253_Leu254insAsn in PLS3 disrupts interaction between PLS3 and its binding partner LCP1 (L-plastin). Both PLS3 and LCP1 regulate intracellular Ca2+ levels, and mutant PLS3 weakens this regulatory function. The PLS3-LCP1 interaction is enhanced under low extracellular Ca2+ concentration. Co-IP/pulldown (binding partner identification), intracellular Ca2+ measurement, mutant vs. wildtype comparison Clinical genetics Medium 28646489
2019 PLS3 overexpression delays ataxic phenotype in Chp1-mutant (vacillator) mice by ameliorating axon hypertrophy and axonal swellings in Purkinje neurons. Mechanistically, PLS3 overexpression trends toward increased membrane targeting/expression of Na+/H+ exchanger NHE1, an important CHP1 binding partner. Transgenic PLS3 overexpression in Chp1 mutant mice, behavioral phenotyping, histological analysis of Purkinje neurons, Western blotting for NHE1 Frontiers in neuroscience Medium 31607845
2023 PLS3 localizes to focal adhesions in osteoblasts and is required for mechanosensitive regulation of osteoblast mineralization. Depletion of PLS3 in MC3T3-E1 cells abolishes cell responsiveness to ECM stiffness (cell size, focal adhesion length, number) and blocks matrix mineralization. Rescue with wildtype but not actin-bundling-deficient PLS3 mutants restores stiffness response, demonstrating actin-bundling is required. Stable KD in preosteoblast cell line (MC3T3-E1), rescue with WT and patient mutants, ECM stiffness substrates (6 vs. 100 kPa), osteogenic differentiation mineralization assay, immunofluorescence FA quantification Frontiers in cell and developmental biology High 38089885
2024 PLS3 loss-of-function in murine MLO-Y4 osteocyte-like cells causes differential expression of Wnt1, Nos1ap, and Myh3, implicating Wnt and Th17 differentiation pathways. ACTN1 and ACTN4 can rescue skeletal deformities in pls3-morphant zebrafish, but FSCN1 cannot, indicating partial functional redundancy among actin bundlers. RNA-seq after Pls3 KD in MLO-Y4 cells, morpholino knockdown in zebrafish with actin-bundler rescue experiments, osteogenic transdifferentiation of patient fibroblasts Cells Medium 39273077
2023 Missense PLS3 variants specifically affecting actin-binding domains cause congenital diaphragmatic hernia (CDH) with gain-of-function effect, whereas loss-of-function variants cause osteoporosis. A mouse knockin model of p.Trp499Cys (within actin-binding domain) recapitulates diaphragm and abdominal-wall defects with increased (not decreased) bone mineral density, demonstrating that distinct variant classes in the actin-binding domains produce opposite functional consequences. In silico protein modeling, mouse knockin model (c.1497G>C; p.Trp499Cys), skeletal phenotyping (BMD), diaphragm/body-wall assessment in mice and human subjects American journal of human genetics High 37751738
2025 PLS3 (and PLS2) functions as a cytoskeletal pH sensor: F-actin bundling activity of PLS3 is reduced at alkaline pH and enhanced at acidic pH, mediated through the N-terminal actin-binding domain (ABD1). In fibroblasts, elevated cytosolic pH causes PLS2 dissociation from actin structures, while acidic conditions promote association with focal adhesions and stress fibers. His207 is identified as a pH-sensing residue in PLS2. In vitro F-actin bundling assays at varying pH, live-cell imaging of pH-induced localization changes, site-directed mutagenesis of His207 bioRxiv (preprint)preprint Medium bio_10.1101_2025.03.26.645573
1999 The T-plastin promoter contains a CCAAT box, Sp1 motif, and four AP2 motifs but no TATA box. Differential expression between leukocytes and non-leukocytes is controlled by CpG island methylation: CpG sites within the island are fully methylated in T-plastin-negative leukemia lines and unmethylated in T-plastin-expressing cells. A T-plastin enhancer composed of two inverted symmetric octamers separated by 17 nucleotides is inactive in leukocytes. S1 mapping (transcription start sites), promoter/enhancer reporter assays, restriction enzyme methylation analysis, DNA footprinting DNA and cell biology High 10025506
2012 Aberrant T-plastin (PLS3) expression in Sézary syndrome cells is associated with promoter hypomethylation of specific CpG dinucleotides (positions 95-99 in the CpG island). T-plastin is expressed only in clonally involved CD3+CD4+CD26- lymphocytes. Pyrosequencing of CpG dinucleotides, RT-PCR for PLS3 expression, immunofluorescence with anti-PLS3 antibody, TCR clonality assay The Journal of investigative dermatology Medium 22495182
2015 Promoter hypomethylation drives PLS3 overexpression in Sézary syndrome. In vitro methylation of the cloned PLS3 promoter suppresses luciferase reporter expression, and treatment of PLS3-negative Jurkat cells with 5-azacytidine (hypomethylating agent) induces PLS3 expression. Pyrosequencing of CpG regions, in vitro promoter methylation + luciferase reporter assay, 5-azacytidine treatment of Jurkat cells The Journal of investigative dermatology High 25806852
2012 T-plastin expression in Sézary syndrome cells is induced by calcium influx (PMA/ionomycin stimulation) and regulated by the calcineurin/NFAT transcription pathway; calcineurin inhibitors suppress both constitutive and calcium-induced T-plastin expression. Constitutive T-plastin expression confers resistance to etoposide-induced apoptosis and promotes cell migration toward CCL17 and IP-10 chemokines. Pharmacological stimulation (PMA/ionomycin), calcineurin inhibitor treatment, apoptosis assay, migration assay Blood Medium 22627769
2024 T-plastin (PLST) promotes epithelial-mesenchymal transition (EMT) in human lung cancer cells via the FAK/AKT/Slug signaling axis; PLST overexpression enhances cell migration and invasion with upregulation of vimentin and Slug and downregulation of E-cadherin, whereas PLST knockdown reverses these effects. Phosphorylation levels of FAK and AKT are dependent on PLST expression. Overexpression and siRNA knockdown, migration/invasion assays, Western blotting for EMT markers and FAK/AKT phosphorylation BMB reports Medium 38835117
2018 Bioinformatic and homology modeling analyses identify a critical LOOP-1 region (residues 240-266) in PLS3 that physically connects the CH1 and CH2 domains of ABD1 and is spatially located at the ABD1-ABD2 interface, essential for actin-binding conformation transition. A novel nonsense mutation (p.E249X) in LOOP-1 truncates the protein and is predicted to disrupt actin binding. Targeted gene sequencing, homology modeling, molecular dynamics simulation International journal of endocrinology Low 30405713
2009 ZNF471 transcriptionally represses PLS3 by directly binding to the PLS3 promoter and recruiting co-repressor KAP1, which induces H3K9me3 enrichment at the PLS3 promoter locus. ChIP-PCR for ZNF471 binding and H3K9me3 at PLS3 promoter, ectopic ZNF471 expression with PLS3 expression readout, co-IP for KAP1 recruitment 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 160 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 132 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 70 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 41 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 39 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
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 29 21426900
2017 PLS3 Mutations in X-Linked Osteoporosis: Clinical and Bone Characteristics of Two Novel Mutations. Hormone research in paediatrics 28 28605746
2012 Inducible expression and pathophysiologic functions of T-plastin in cutaneous T-cell lymphoma. Blood 27 22627769
2022 Structural mechanism for bidirectional actin cross-linking by T-plastin. Proceedings of the National Academy of Sciences of the United States of America 26 36067297
2020 T-Plastin reinforces membrane protrusions to bridge matrix gaps during cell migration. Nature communications 26 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 26 27732335
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
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 25 31968132
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
2016 Atypical femur fracture in an adolescent boy treated with bisphosphonates for X-linked osteoporosis based on PLS3 mutation. Bone 22 27477003
2018 A novel frameshift deletion in PLS3 causing severe primary osteoporosis. Journal of human genetics 21 29884797
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 18 32453450
2014 T-plastin expression downstream to the calcineurin/NFAT pathway is involved in keratinocyte migration. PloS one 18 25226517
2017 Hypoxia-stimulated membrane trafficking requires T-plastin. Acta physiologica (Oxford, England) 17 28218996
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 14 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 12 28646489
2021 X-Linked Osteogenesis Imperfecta Possibly Caused by a Novel Variant in PLS3. Genes 11 34946798
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
2015 Expression of the PLS3 Gene in Circulating Cells in Patients with Colorectal Cancer. Polski przeglad chirurgiczny 10 26146096
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
2022 Identification of a novel splicing mutation and genotype-phenotype correlations in rare PLS3-related childhood-onset osteoporosis. Orphanet journal of rare diseases 8 35752817
2023 The intricate mechanism of PLS3 in bone homeostasis and disease. Frontiers in endocrinology 7 37484945
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
2023 Impaired bone strength and bone microstructure in a novel early-onset osteoporotic rat model with a clinically relevant PLS3 mutation. eLife 6 37083757
2019 PLS3 Overexpression Delays Ataxia in Chp1 Mutant Mice. Frontiers in neuroscience 6 31607845
2023 PLS3 missense variants affecting the actin-binding domains cause X-linked congenital diaphragmatic hernia and body-wall defects. American journal of human genetics 5 37751738
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
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 4 39658012
2023 PLS3 promotes papillary thyroid carcinoma progression by activating the Notch signaling pathway. Environmental toxicology 4 37347555
2024 T-plastin contributes to epithelial-mesenchymal transition in human lung cancer cells through FAK/AKT/Slug axis signaling pathway. BMB reports 3 38835117
2024 Early-Onset Osteoporosis: Molecular Analysis in Large Cohort and Focus on the PLS3 Gene. Calcified tissue international 3 39316135
2022 Lipocalin-2 is associated with FGF23 in WNT1 and PLS3 osteoporosis. Frontiers in endocrinology 3 36157448
2024 Functional Insights in PLS3-Mediated Osteogenic Regulation. Cells 2 39273077
2023 The actin-bundling protein, PLS3, is part of the mechanoresponsive machinery that regulates osteoblast mineralization. Frontiers in cell and developmental biology 2 38089885
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