scholarly journals Control of vertebrate core planar cell polarity protein localization and dynamics by Prickle 2

Development ◽  
2015 ◽  
Vol 142 (19) ◽  
pp. 3429-3439 ◽  
Author(s):  
Mitchell T. Butler ◽  
John B. Wallingford
2021 ◽  
Author(s):  
Mohd. Suhail Rizvi ◽  
Divyoj Singh ◽  
Mohit Kumar Jolly

Planar Cell Polarity (PCP), characterized by asymmetric localization of proteins at the cell membrane within the epithelial plane, plays essential roles in embryonic development and physiological functions. The significance of PCP can be appreciated by the outcomes of PCP failure in the form of defects in neural tube formation, tracheal malfunctions, organ shape misregulation, hair follicle misalignment etc. Extensive experimental works on PCP in fruit fly Drosophila melanogaster have classified the proteins involved in PCP into two modules: 'core' module, acting locally by inter-cellular protein interactions, and, 'global' module, responsible for the alignment of cell polarities with that of the tissue axis. Despite the involvement of different molecular players, the asymmetric localization of the proteins of the two modules on cell membrane primarily involve inter-cellular dimer formations. We have developed a continuum model of the localization of PCP proteins on the cell membrane and its regulation via intra- and inter-cellular protein-protein interactions. We have identified the conditions for the asymmetric protein localization, or PCP establishment, for uniform and graded protein expression levels in the tissue. We have found that in the absence of any tissue level expression gradient the polarized state of the tissue is not stable against finite length perturbations which is also a property of the active polar matter. However, in the presence of tissue level expression gradients of proteins the polarized state remains stable. We have also looked at the influence of the loss of PCP proteins from a select regions of the tissue on the polarization of the cells outside of that region. This continuum theory of the planar cell polarity can be coupled with the active matter hydrodynamics to study the cell flows and their regulation by genetic machinery.


2018 ◽  
Vol 217 (5) ◽  
pp. 1633-1641 ◽  
Author(s):  
Sun K. Kim ◽  
Siwei Zhang ◽  
Michael E. Werner ◽  
Eva J. Brotslaw ◽  
Jennifer W. Mitchell ◽  
...  

Most epithelial cells polarize along the axis of the tissue, a feature known as planar cell polarity (PCP). The initiation of PCP requires cell–cell signaling via the noncanonical Wnt/PCP pathway. Additionally, changes in the cytoskeleton both facilitate and reflect this polarity. We have identified CLAMP/Spef1 as a novel regulator of PCP signaling. In addition to decorating microtubules (MTs) and the ciliary rootlet, a pool of CLAMP localizes at the apical cell cortex. Depletion of CLAMP leads to the loss of PCP protein asymmetry, defects in cilia polarity, and defects in the angle of cell division. Additionally, depletion of CLAMP leads to a loss of the atypical cadherin-like molecule Celrs2, suggesting that CLAMP facilitates the stabilization of junctional interactions responsible for proper PCP protein localization. Depletion of CLAMP also affects the polarized organization of MTs. We hypothesize that CLAMP facilitates the establishment of cell polarity and promotes the asymmetric accumulation of MTs downstream of the establishment of proper PCP.


2014 ◽  
Vol 207 (2) ◽  
pp. 171-179 ◽  
Author(s):  
Danelle Devenport

Planar cell polarity (PCP) refers to the coordinated alignment of cell polarity across the tissue plane. Key to the establishment of PCP is asymmetric partitioning of cortical PCP components and intercellular communication to coordinate polarity between neighboring cells. Recent progress has been made toward understanding how protein transport, endocytosis, and intercellular interactions contribute to asymmetric PCP protein localization. Additionally, the functions of gradients and mechanical forces as global cues that bias PCP orientation are beginning to be elucidated. Together, these findings are shedding light on how global cues integrate with local cell interactions to organize cellular polarity at the tissue level.


eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Erin Newman-Smith ◽  
Matthew J Kourakis ◽  
Wendy Reeves ◽  
Michael Veeman ◽  
William C Smith

The Ciona notochord displays planar cell polarity (PCP), with anterior localization of Prickle (Pk) and Strabismus (Stbm). We report that a myosin is polarized anteriorly in these cells and strongly colocalizes with Stbm. Disruption of the actin/myosin machinery with cytochalasin or blebbistatin disrupts polarization of Pk and Stbm, but not of myosin complexes, suggesting a PCP-independent aspect of myosin localization. Wash out of cytochalasin restored Pk polarization, but not if done in the presence of blebbistatin, suggesting an active role for myosin in core PCP protein localization. On the other hand, in the pk mutant line, aimless, myosin polarization is disrupted in approximately one third of the cells, indicating a reciprocal action of core PCP signaling on myosin localization. Our results indicate a complex relationship between the actomyosin cytoskeleton and core PCP components in which myosin is not simply a downstream target of PCP signaling, but also required for PCP protein localization.


Development ◽  
2021 ◽  
Author(s):  
Lena P. Basta ◽  
Michael Hill-Oliva ◽  
Sarah V. Paramore ◽  
Rishabh Sharan ◽  
Audrey Goh ◽  
...  

The collective polarization of cellular structures and behaviors across a tissue plane is a near universal feature of epithelia known as planar cell polarity (PCP). This property is controlled by the core PCP pathway, which is comprised of highly conserved membrane-associated protein complexes that localize asymmetrically at cell junctions. Here we introduce three new mouse models for investigating the localization and dynamics of transmembrane PCP proteins Celsr1, Fz6, and Vangl2. Using the skin epidermis as a model, we characterize and verify the expression, localization and function of endogenously-tagged Celsr1-3xGFP, Fz6-3xGFP and tdTomato-Vangl2 fusion proteins. Live imaging of Fz6-3xGFP in basal epidermal progenitors reveals that the polarity of the tissue is not fixed through time. Rather asymmetry dynamically shifts during cell rearrangements and divisions, while global, average polarity of the tissue is preserved. We show using super-resolution STED imaging that Fz6-3xGFP and tdTomato-Vangl2 can be resolved, enabling us to observe their complex localization along junctions. We further explore PCP fusion protein localization in the trachea and neural tube, and discover new patterns of PCP expression and localization throughout the mouse embryo.


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