Affinage

WDPCP

WD repeat-containing and planar cell polarity effector protein fritz homolog · UniProt O95876

Length
746 aa
Mass
85.1 kDa
Annotated
2026-04-28
22 papers in source corpus 11 papers cited in narrative 13 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

WDPCP is a WD40-repeat-containing planar cell polarity (PCP) effector protein that functions downstream of core PCP components to organize the actin cytoskeleton, regulate ciliogenesis, and promote Hedgehog signaling. At the ciliary transition zone, WDPCP recruits Sept2, Nphp1, and Mks1 to enable ciliogenesis and Hedgehog pathway activation, with residues D481/W482 essential for apical docking and ciliogenic function (PMID:24302887, PMID:41268724, PMID:34225660). In the cytoplasm, WDPCP interacts with Sept2 at actin filaments and focal adhesions to control actin organization, cortical tension, cell polarity, and directional migration—functions that operate independently of cilia, as demonstrated by intact kinocilia in Wdpcp-mutant cochlea (PMID:24302887, PMID:25436430). WDPCP also promotes epithelial-mesenchymal transition via the MAPK/ERK signaling axis, a function required for coronary artery smooth muscle development and cardiac microvascular endothelial cell migration (PMID:29487191, PMID:39582775).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 2005 High

    Identification of Fritz (Drosophila WDPCP ortholog) as a cell-autonomous PCP effector established that a WD40/coiled-coil protein functions downstream of Frizzled to organize cytoskeletal polarity at hair initiation sites.

    Evidence Drosophila loss-of-function mutants with clonal and epistasis analyses in wing cells

    PMID:15654087

    Open questions at the time
    • Mammalian function not yet tested
    • Direct binding partners unidentified
    • Mechanism of actin reorganization unknown
  2. 2013 High

    Demonstration that WDPCP localizes to both the ciliary transition zone and the actin cytoskeleton/focal adhesions, and recruits Sept2, Nphp1, and Mks1 to the transition zone, unified its dual roles in ciliogenesis and actin-based polarity.

    Evidence Wdpcp knockout mouse; co-immunoprecipitation of WDPCP–Sept2; immunofluorescence for transition zone and actin markers; migration assays

    PMID:24302887

    Open questions at the time
    • Structural basis for WDPCP–Sept2 interaction unknown
    • How WDPCP is itself recruited to the transition zone not defined
  3. 2013 High

    Showing that PCP defects in Wdpcp-mutant cochlea occur despite normal kinocilia separated the actin-organizing function of WDPCP from its ciliogenic role, establishing cilia-independent polarity regulation.

    Evidence Wdpcp knockout mouse cochlear hair cell analysis with kinocilia and PCP marker examination

    PMID:24302887

    Open questions at the time
    • Signaling intermediate linking WDPCP to PCP effectors in the inner ear not identified
    • Whether cilia-independent polarity function is conserved in other tissues unclear
  4. 2014 Medium

    Fritz/WDPCP was shown to physically interact with other PPE proteins (Inturned, Fuzzy) and Dishevelled, and to maintain cortical rigidity via actomyosin/septin control, revealing its position as a node linking upstream PCP signals to cortical mechanics.

    Evidence Co-immunoprecipitation in Drosophila; Xenopus mucociliary epithelium live imaging; septin localization and actomyosin inhibition experiments

    PMID:25072625 PMID:25436430

    Open questions at the time
    • Whether Inturned/Fuzzy interactions are conserved in mammals not tested
    • Direct versus bridged nature of these interactions not resolved
  5. 2017 Medium

    Extension to human airway epithelium confirmed WDPCP is required for ciliogenesis and Septin7 expression in primary sinonasal cells, and a direct Fritz–Dishevelled interaction was demonstrated, solidifying WDPCP as a PCP-to-cilia signal relay.

    Evidence siRNA knockdown in air-liquid interface cultured human sinonasal epithelial cells; Co-IP and CRISPR-tagged Fritz in Drosophila wing

    PMID:28001338 PMID:28258110

    Open questions at the time
    • Mechanism by which WDPCP regulates septin expression versus localization not distinguished
    • Dishevelled interaction not confirmed in mammalian cells
  6. 2018 High

    Tissue-specific deletion revealed WDPCP promotes epicardial EMT and migration required for coronary artery smooth muscle coverage, establishing a developmental role beyond canonical ciliogenesis.

    Evidence Epicardium-specific Cre-lox deletion in mouse; EMT and mesenchymal marker expression; cell migration assays

    PMID:29487191

    Open questions at the time
    • Whether EMT function depends on cilia or is cilia-independent not formally tested
    • Downstream transcriptional targets of WDPCP in EMT not catalogued
  7. 2021 High

    Conditional limb mesenchyme knockout showed WDPCP is a positive regulator of Hedgehog signaling required for chondrogenic and osteogenic differentiation, while airway studies linked WDPCP to MAPK/ERK-dependent cilia beating and mitochondrial biogenesis.

    Evidence Prx1-Cre conditional KO with Hh marker analysis and growth plate histology; siRNA knockdown in sinonasal ALI cultures with U0126 MAPK inhibition and mitochondrial assays

    PMID:33598458 PMID:34225660

    Open questions at the time
    • Whether WDPCP acts on Hh signaling purely via cilia or also intracellularly not resolved
    • Link between MAPK/ERK and mitochondrial function through WDPCP is correlative
  8. 2024 Medium

    The WDPCP–MAPK/ERK axis was shown to mediate EMT and migration in cardiac microvascular endothelial cells, with leucine-induced WDPCP suppression causing vascular dysfunction rescuable by WDPCP overexpression.

    Evidence High-leucine mouse model; WDPCP overexpression and MAPK activation rescue in HCMECs; EMT marker and endomucin expression analysis

    PMID:39582775

    Open questions at the time
    • Mechanism by which leucine suppresses WDPCP expression unknown
    • In vivo cardiovascular phenotype from endothelial-specific WDPCP loss not shown
  9. 2025 High

    Identification of D481/W482 as essential residues for apical docking and ciliogenesis provided the first structure–function insight into WDPCP, showing that conformational integrity at an alpha-helix junction is required for its ciliogenic and Hh signaling functions.

    Evidence Wdpcp-Z11 knock-in mouse; rescue by reintroduction of D481/W482; AlphaFold structure prediction; immunofluorescence for cilia and Hh markers

    PMID:41268724

    Open questions at the time
    • No experimental high-resolution structure available
    • Binding partner that recognizes the D481/W482 surface not identified
    • Whether these residues affect actin/PCP functions not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the molecular basis of WDPCP apical targeting and transition zone anchoring, whether its EMT and MAPK/ERK functions are cilia-dependent or -independent, and the identity of the direct binding surface recognized by D481/W482.
  • No experimental 3D structure of WDPCP
  • Cilia-dependent versus -independent EMT regulation not formally separated
  • Upstream signals controlling WDPCP expression and localization largely uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 4 GO:0060090 molecular adaptor activity 4
Localization
GO:0005856 cytoskeleton 3 GO:0005886 plasma membrane 3 GO:0005929 cilium 3
Pathway
R-HSA-162582 Signal Transduction 6 R-HSA-1852241 Organelle biogenesis and maintenance 3 R-HSA-1266738 Developmental Biology 2
Partners
DVLFUZINTUMKS1NPHP1SEPT2SEPT7

Evidence

Reading pass · 13 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2013 WDPCP localizes to the ciliary transition zone, where it is required for recruitment of Sept2, Nphp1, and Mks1; loss of WDPCP causes failure of these proteins to localize to the transition zone, impairing ciliogenesis. Wdpcp knockout mouse model; immunofluorescence localization; loss-of-function phenotypic analysis PLoS Biology High 24302887
2013 WDPCP localizes to the actin cytoskeleton and focal adhesions in the cytoplasm, where it interacts with Sept2 and is required for Sept2 recruitment to actin filaments; Wdpcp deficiency disrupts actin filament organization, focal contacts, membrane ruffling, cell polarity, and directional cell migration. Co-immunoprecipitation/co-localization; Wdpcp knockout mouse fibroblasts; actin staining; focal adhesion assays; migration assays PLoS Biology High 24302887
2013 PCP defects in Wdpcp mutant cochlea occur despite normal kinocilia, indicating Wdpcp regulates planar cell polarity via direct modulation of the actin cytoskeleton rather than through cilia. Wdpcp knockout mouse; cochlear hair cell analysis; kinocilia and PCP marker examination PLoS Biology High 24302887
2005 Drosophila Fritz (ortholog of WDPCP), a coiled-coil WD40 protein, functions cell-autonomously downstream of core PCP proteins (Frizzled) to regulate the location and number of wing cell prehair initiation sites by organizing actin cytoskeletal polarity. Drosophila genetics; clonal analysis; epistasis experiments; loss-of-function mutants Genetics High 15654087
2014 WDPCP (Fritz) is required for basolateral plasma membrane stability and cortical rigidity in epithelial cells by controlling cortical septin localization and acting via actomyosin to maintain balanced cortical tension. In vivo 3D time-lapse imaging; Xenopus mucociliary epithelium; septin localization assays; actomyosin inhibition experiments Biochemical and Biophysical Research Communications Medium 25436430
2014 Drosophila Fritz (WDPCP ortholog) physically interacts with Inturned and Fuzzy (other PPE proteins), and when overexpressed can repatterning the accumulation of upstream PCP proteins (e.g., Frizzled), indicating context-dependent feedback in the PCP hierarchy. Co-immunoprecipitation; genetic overexpression; immunofluorescence in Drosophila wing Developmental Biology Medium 25072625
2017 Drosophila Fritz (WDPCP ortholog) directly interacts with Dishevelled, providing a potential mechanistic link by which upstream PCP core proteins instruct PPE protein accumulation; Fritz also shows In-independent PCP activity. Co-immunoprecipitation; genetic rescue of inturned deletion; CRISPR/Cas9-tagged Fritz live imaging in Drosophila wing G3 (Bethesda) Medium 28258110
2018 Wdpcp promotes epicardial epithelial-mesenchymal transition (EMT) and epicardium-derived cell (EPDC) migration required for coronary artery smooth muscle coverage; epicardium-specific deletion of Wdpcp recapitulates the coronary artery defect, and Wdpcp mutant hearts show enhanced chemotactic responses to Shh. Tissue-specific Cre-lox deletion (Wdpcp epicardium-specific KO); immunofluorescence; EMT/mesenchymal marker expression; cell migration assays Science Signaling High 29487191
2021 Loss of Wdpcp in limb bud mesenchyme (via Prx1-Cre) abolishes hedgehog signaling responsiveness, impairs chondrogenic and osteogenic differentiation, and disrupts growth plate organization, placing Wdpcp as a positive regulator of Hh pathway activity in skeletal progenitors. Conditional KO (Prx1-Cre); in vitro chondrogenesis and osteogenesis assays; Hh signaling marker expression; growth plate histology BMC Developmental Biology High 34225660
2021 WDPCP regulates cilia beating in sinonasal epithelial cells via the MAPK/ERK pathway; WDPCP knockdown impairs mitochondrial biogenesis and function, which can be partially restored by dexamethasone. Air-liquid interface culture; siRNA knockdown; MAPK/ERK pathway inhibition (U0126); mitochondrial function assays Frontiers in Cell and Developmental Biology Medium 33598458
2017 WDPCP is required for ciliogenesis in human sinonasal epithelial cells; knockdown of WDPCP reduces cilia quantity and length and decreases Septin7 expression in an air-liquid interface model. siRNA knockdown in primary human sinonasal epithelial cells; air-liquid interface culture; immunofluorescence for cilia and Septin7 Cytoskeleton (Hoboken) Medium 28001338
2025 Residues D481 and W482 (human N512/W513) in WDPCP are essential for its docking to the apical cell surface and for ciliogenesis and Hh signaling; structure predictions place these residues at the junction of two alpha helices in WDPCP, and their deletion impairs protein conformational stability without abolishing expression. Genetically engineered mouse model (Wdpcp-Z11); rescue experiments with reintroduction of D481/W482; structure prediction; immunofluorescence for cilia and Hh signaling markers Disease Models & Mechanisms High 41268724
2024 High leucine levels suppress WDPCP expression and attenuate MAPK/ERK signaling in cardiac microvascular endothelial cells, impairing EMT and cell migration; overexpression of WDPCP or MAPK activation rescues these defects, and the WDPCP/MAPK axis regulates endomucin (EMCN) upregulation induced by high leucine. High-leucine mouse model; WDPCP overexpression and MAPK activation in HCMECs; EMT marker expression; migration assays; EMCN expression analysis Pulmonary Circulation Medium 39582775

Source papers

Stage 0 corpus · 22 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 Wdpcp, a PCP protein required for ciliogenesis, regulates directional cell migration and cell polarity by direct modulation of the actin cytoskeleton. PLoS biology 92 24302887
1997 Fritz: a secreted frizzled-related protein that inhibits Wnt activity. Mechanisms of development 61 9178261
2005 The WD40 repeat protein fritz links cytoskeletal planar polarity to frizzled subcellular localization in the Drosophila epidermis. Genetics 48 15654087
1993 17th Fritz Lipmann Lecture. Wanderings (wonderings) in metabolism. Biological chemistry Hoppe-Seyler 37 8267876
2014 Compound heterozygosity for a frame shift mutation and a likely pathogenic sequence variant in the planar cell polarity—ciliogenesis gene WDPCP in a girl with polysyndactyly, coarctation of the aorta, and tongue hamartomas. American journal of medical genetics. Part A 24 25427950
2006 Fritz Verzár was born 120 years ago: his contribution to experimental gerontology through the collagen research as assessed after half a century. Archives of gerontology and geriatrics 19 16764955
2018 Wdpcp promotes epicardial EMT and epicardium-derived cell migration to facilitate coronary artery remodeling. Science signaling 16 29487191
2014 The planar cell polarity effector protein Wdpcp (Fritz) controls epithelial cell cortex dynamics via septins and actomyosin. Biochemical and biophysical research communications 16 25436430
2014 The proteins encoded by the Drosophila Planar Polarity Effector genes inturned, fuzzy and fritz interact physically and can re-pattern the accumulation of "upstream" Planar Cell Polarity proteins. Developmental biology 12 25072625
2021 WDPCP Modulates Cilia Beating Through the MAPK/ERK Pathway in Chronic Rhinosinusitis With Nasal Polyps. Frontiers in cell and developmental biology 9 33598458
2017 WDPCP regulates the ciliogenesis of human sinonasal epithelial cells in chronic rhinosinusitis. Cytoskeleton (Hoboken, N.J.) 9 28001338
2023 Evidence for involvement of the alcohol consumption WDPCP gene in lipid metabolism, and liver cirrhosis. Scientific reports 7 37996473
2021 Wdpcp regulates cellular proliferation and differentiation in the developing limb via hedgehog signaling. BMC developmental biology 7 34225660
2017 Planar Cell Polarity Effector Fritz Interacts with Dishevelled and Has Multiple Functions in Regulating PCP. G3 (Bethesda, Md.) 7 28258110
2022 Ancylobacter moscoviensis sp. nov., novel facultatively methylotrophic bacteria from activated sludge and the reclassification of Starkeya novella (Starkey 1934) Kelly et al. 2000 as Ancylobacter novellus comb. nov., Starkeya koreensis Im et al. 2006 as Ancylobacter koreensis comb.nov., Angulomicrobium tetraedrale Vasil'eva et al. 1986 as Ancylobacter tetraedralis comb. nov., Angulomicrobium amanitiforme Fritz et al. 2004 as Ancylobacter amanitiformis comb. nov., and Methylorhabdus multivorans Doronina et al. 1996 as Ancylobacter multivorans comb. nov., and emended description of the genus Ancylobacter. Antonie van Leeuwenhoek 5 36462112
2006 An original approach to aging: an appreciation of Fritz Verzár's contribution in the light of the last 50 years of gerontological facts and thinking. Gerontology 3 16974097
2024 High gestational leucine level dampens WDPCP/MAPK signaling to impair the EMT and migration of cardiac microvascular endothelial cells in congenital heart defects. Pulmonary circulation 2 39582775
2024 A cross-tissue transcriptome-wide association study identifies WDPCP as a potential susceptibility gene for coronary atherosclerosis. Atherosclerosis plus 1 39669798
2022 Development and Heredity in the Interwar Period: Hans Spemann and Fritz Baltzer on Organizers and Merogones. Journal of the history of biology 1 35930095
2025 The magic bullet: a tribute to Fritz Eckstein. Nucleosides, nucleotides & nucleic acids 0 40326535
2025 Identification of conserved residues essential for the ciliogenic functions of WDPCP. Disease models & mechanisms 0 41268724
2019 Lillian Fritz-Laylin: Keeping up to speed with evolutionary cell biology. The Journal of cell biology 0 30914418