Vertebrate Wnt/planar cell polarity (PCP) signalling - Wnt5a/Wnt11, ROR2/PTK7, core PCP complexes and Rho/Rac effector arms

Planar cell polarity (PCP) orients cells within the plane of a tissue. It is needed for convergent extension during gastrulation, neural tube closure, orientation of inner-ear hair-cell bundles and hair follicles, and limb elongation. In vertebrates the system is set up by Wnt ligands, chiefly Wnt5a and Wnt11, which do not stabilize beta-catenin in most contexts. They act through Frizzled receptors with the ROR2 and PTK7 co-receptors and induce dose-dependent phosphorylation of the four-pass membrane protein VANGL2. The core PCP proteins form two mutually exclusive membrane complexes at opposite sides of each cell. One is Frizzled with Dishevelled, recruited through its DEP domain to the Frizzled tail. The other is VANGL with Prickle, which binds Dishevelled and antagonizes its recruitment by Frizzled. The atypical cadherin CELSR1 forms homophilic bridges between neighbouring cells and recruits both sides to the junction. Dishevelled drives two effector arms: the formin DAAM1 links it to RhoA and Rho kinase for actomyosin contractility, and Rac1 activates JNK. Together they turn polarity cues into oriented cytoskeletal behaviour and cell movement. The pathway works independently of the beta-catenin destruction complex and TCF/LEF transcription.

Derived from RGD PW:0000200 (wnt signaling, the planar cell polarity pathway; 16 RGD-curated human genes: CELSR1, DAAM1, DVL1, DVL2, FZD3, FZD6, FZD7, FZD9, PRICKLE1, PRICKLE2, PTK7, RAC1, RHOA, SCRIB, VANGL2, WNT7B). The PCP Frizzleds (FZD3, FZD6, FZD7) enter through the referenced generic receptor step and are named in prose. Every other RGD gene except SCRIB, FZD9 and WNT7B is a part or a representative member. Added beyond RGD: WNT5A, WNT11, ROR2, VANGL1 and the ROCK and JNK kinases that complete the effector arms named by RGD's subpathway links (PW:0000105 Rho/Rac/Cdc42, PW:0000313 JNK MAPK; mentioned here only, not claimed as evidence). GO terms: the RGD-mapped GO:0060071 and its regulation terms (GO:2000095, GO:2000096) are proposed for obsoletion in GO's PCP restructuring (ai4curation/ai-gene-review#5781, upstream geneontology/go-annotation#6638 and go-ontology#32697). The module therefore uses GO:0001736 establishment of planar polarity (to be redefined, not retired) and the parent GO:0035567 non-canonical Wnt signaling pathway as concepts, and no annoton uses a term on the retirement list. The upstream-proposed core PCP module term (written there as GO:7770140) is not in GO release 2026-07-26 and is not used; once it exists it is the natural module concept. Reuse of the generic wnt_signaling module: ligand acylation and secretion and the Frizzled receptor step are included by module_ref. The receptor node carries an EXACTLY_ONE co-receptor choice whose LRP5/6 variant is canonical, so the PCP co-receptors ROR2 and PTK7 are made concrete in a separate step. Dishevelled could not be referenced: in wnt_signaling it sits on the branch-transduction node together with the canonical branch and a coarse PCP branch, so a reference would let canonical signalling satisfy this module and would nest a sketch of this module inside itself. Dishevelled is therefore restated only in its PCP-specific capacity (DEP-domain recruitment to Frizzled) with the same signalling-adaptor function. Boundary with canonical signalling: LRP5/6, Axin, APC, GSK3, beta-catenin and TCF/LEF are outside the module; DAAM1 and Rac1 act without affecting beta-catenin (PMID:11779461, PMID:12533515). PTK7 also has a reported canonical beta-catenin-binding role, which is its core function in the gene review, and here only its PCP co-receptor role is modelled. Left out: SCRIB (RGD draws a Scrib-Vangl2 association; no cached primary source was available to ground it, so it is noted rather than modelled); ANKRD6 (Diego), a Frizzled-side cytoplasmic core protein not in the RGD list; FZD9 and WNT7B (RGD-listed but with weak PCP-specific evidence); the Fat/Dachsous system, the PCP effector/CPLANE proteins (INTU, FUZ, WDPCP) and ciliary PCP outputs; Wnt/calcium signalling, which is the other non-canonical branch in wnt_signaling. Several core proteins (VANGL, PRICKLE, CELSR1) are given no molecular function, because GOA has only binding or electronic functions for the human proteins and GO has no term for a scaffold that partitions to one side of the cell. GO-CAM: no model in gocams/index.tsv is a PCP model. The seed's best GO-CAM lead (gomodel:62900b6400001749, ZDHHC7 regulating SCRIB in polarized epithelial differentiation) overlaps only through SCRIB, is about apical-basal polarity and is not linked. RHOA, RAC1 and MAPK8 appear in many human models for unrelated pathways, and none of them is linked.