Description
The planar cell polarity Wnt signaling pathway (PCP) plays a major role in embryonic tissue patterning, cell polarization, migration and morphogenesis. The PCP pathway, along with the Wnt-calcium pathway, belongs to the non-canonical Wnt signaling in that is independent of beta-catenin, the core component of the canonical Wnt pathway. The PCP pathway is less well understood and characterized but evidence is rapidly accumulating establishing the core components and the role they play, the common denominators and the distinctions between Drosophila and vertebrates. Frizzled receptors (Fzd) and the intracellular dishevelled (Dvl), the latter representing the branching point between canonical and non-canonical pathways, are necessary components. A requirement for Wnt ligands is controversial but some, like Wnt5, Wnt7 and Wnt11 appear to play a role, at least in vertebrates. Other core components include the membrane proteins Vangl2 (Strabismus/Van Gogh homolog) and Celsr1 (Flamingo homolog) and the cytoplasmic Prickle. Additional members of the vertebrate PCP pathway include Ptk7 and Scrib and the downstream effector Daam1. The asymmetric and polarized membrane association of PCP components has been established in Drosophila; a similar, yet distinct pattern has been observed in mammals. Scrib interacting with Vangl2 plays a role in the asymmetric positioning of Vangl2 (interaction mediated by the
PDZ domains of the two proteins, a domain also shared by the modular dishevelled); Celsr1 also contributes to the asymmetric localization of Vangl2. Vangl can recruit Prickle which then can bind to and antagonize Dvl recruitment by Fzd. Activation of Fzd and recruitment of Dvl leads to activation of the members of the Rho family of small monomeric G proteins RhoA – via interaction with Daam1, and Rac and subsequent triggering of Rho/Rac/Cdc42 and C-Jun N-terminal kinase (JNK) pathways. The former pathway controls cytoskeletal rearrangements and organization and the latter impacts on gene expression. Deregulation of the pathway has been implicated in a number of human diseases including cancer.
To see the ontology report for annotations, GViewer and download, click here
Abbreviations
Wnt – wingless related family of proteins
Fzd – frizzled homolog family of proteins
Dvl – dishevelled, dsh homolog family of proteins
Vangl2 – vang-like 2 (van gogh, Drosophila)
Celsr1 - cadherin, EGF LAG seven-pass G-type receptor 1 (flamingo homolog, Drosophila) Prickle – prickle homolog family of proteins
Ptk7 - PTK7 protein tyrosine kinase 7
Scrib – scribbled homolog (Drosophila)
Daam1 - dishevelled associated activator of morphogenesis 1
RhoA - ras homolog gene family, member A
Rac1 - ras-related C3 botulinum toxin substrate 1
References PMID:12967557, 16212491, 16192308, 16776590, 16765615, 17230199, 17226800, 17540029
