Cell cortex regulation by the planar cell polarity protein Prickle1

Abstract

The planar cell polarity pathway regulates cell polarity, adhesion, and rearrangement. Its cytoplasmic core components Prickle (Pk) and Dishevelled (Dvl) often localize as dense puncta at cell membranes to form antagonizing complexes and establish cell asymmetry. In vertebrates, Pk and Dvl have been implicated in actomyosin cortex regulation, but the mechanism of how these proteins control cell mechanics is unclear. Here we demonstrate that in Xenopus prechordal mesoderm cells, diffusely distributed, cytoplasmic Pk1 up-regulates the F-actin content of the cortex. This counteracts cortex down-regulation by Dvl2. Both factors act upstream of casein kinase II to increase or decrease cortical tension. Thus, cortex modulation by Pk1 and Dvl2 is translated into mechanical force and affects cell migration and rearrangement during radial intercalation in the prechordal mesoderm. Pk1 also forms puncta and plaques, which are associated with localized depletion of cortical F-actin, suggesting opposite roles for diffuse and punctate Pk1.

Spatially resolved proteomics of the stomatal lineage: polarity complexes for cell divisions and stomatal pores

“…CKA1 and CKB1, our top hits after employing AlphaFold-multimer prediction models (Figure S5), form an especially active CKII in Arabidopsis [69]. Consequently, CKII could phosphorylate OPL2 (as we argue below), but also act downstream of OPL2 or be regulated by OPL2, similar to the situation with CKII and Prk [68]. Although the plant and animal kingdom evolved separately, it is fascinating to compare how proteins from different kingdoms with structurally similar domains behave.…”

“…Although OPL2 does not possess LIM domains, the predicted zinc finger could serve a similar function in mediating protein-protein and cytoskeleton interactions [67]. Likewise, CKII, a protein kinase conserved in all eukaryotes [21], can phosphorylate Dsh [38] but is also itself repressed by Dsh2 and activated by Prk [68] (Figure 7). CKII has many targets throughout eukaryotes and was enriched in our OPL2 proximity-labeling samples (Figure S3).…”

“…Figure 7: Model for OPL2 and partners during cell division and stomatal pore formationThe subcellular distribution of polarity proteins and partners during critical stomatal lineage divisions is cartooned, with a special emphasis on the relationships to microtubule (pink) distribution at different cell cycle phases and during stomatal differentiation. The proposed complex of polarity proteins as defined by proximity labeling and structural modeling is at the bottom, and a comparison to animal protein complexes involved in division orientation and cell polarity boxed[38,65,67,68]. In both systems, IDR-containing molecules assemble into scaffolding complexes that have the potential to interact with intracellular signaling systems.…”

Wnt/planar cell polarity signaling controls morphogenetic movements of gastrulation and neural tube closure

“…Accordingly, inappropriate functioning of Prickle1 causes CE defects, likely by disrupting Fzd-dependent membrane recruitment of Dvl [59]. Intriguingly, recent studies suggest that diffusely distributed cytoplasmic Prickle1 counteracts the activity of Dvl2 to increase F-actin content and cortical tension in Xenopus prechordal mesoderm cells, thereby generating mechanical forces to promote cell migration and rearrangements during radial cell intercalations [22].…”

“…there is increasing evidence that several "core" PCP proteins also mediate radial cell intercalation and contribute to the establishment of apico-basal polarity [22,23,24]. Dysfunctions of PCP regulators (herein referred to as proteins involved in Wnt/PCP signaling) are closely linked to the congenital disorder of neural tube defects (NTDs), such as spina bifida and anencephaly [25,26].…”