scholarly journals Mechanical heterogeneity along single cell-cell junctions is driven by lateral clustering of cadherins during vertebrate axis elongation

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Robert J Huebner ◽  
Abdul Naseer Malmi-Kakkada ◽  
Sena Sarikaya ◽  
Shinuo Weng ◽  
D Thirumalai ◽  
...  
Keyword(s):  
Cell Biology ◽  
Planar Cell Polarity ◽  
Protein Localization ◽  
Tissue Level ◽  
Cell Junctions ◽  
Convergent Extension ◽  
Length Scales ◽  
Mechanical Heterogeneity ◽  
Multiple Length Scales ◽  
Cell Cell

Morphogenesis is governed by the interplay of molecular signals and mechanical forces across multiple length scales. The last decade has seen tremendous advances in our understanding of the dynamics of protein localization and turnover at sub-cellular length scales, and at the other end of the spectrum, of mechanics at tissue-level length scales. Integrating the two remains a challenge, however, because we lack a detailed understanding of the subcellular patterns of mechanical properties of cells within tissues. Here, in the context of the elongating body axis of Xenopus embryos, we combine tools from cell biology and physics to demonstrate that individual cell-cell junctions display finely-patterned local mechanical heterogeneity along their length. We show that such local mechanical patterning is essential for the cell movements of convergent extension and is imparted by locally patterned clustering of a classical cadherin. Finally, the patterning of cadherins and thus local mechanics along cell-cell junctions are controlled by Planar Cell Polarity signaling, a key genetic module for CE that is mutated in diverse human birth defects.

scholarly journals Mechanical heterogeneity along single cell-cell junctions is driven by lateral clustering of cadherins during vertebrate axis elongation

2020 ◽  
Author(s):  
Robert J. Huebner ◽  
Abdul Naseer Malmi-Kakkada ◽  
Sena Sarikaya ◽  
Shinuo Weng ◽  
D. Thirumalai ◽  
...  
Keyword(s):  
Cell Biology ◽  
Planar Cell Polarity ◽  
Protein Localization ◽  
Tissue Level ◽  
Cell Junctions ◽  
Convergent Extension ◽  
Length Scales ◽  
Mechanical Heterogeneity ◽  
Multiple Length Scales ◽  
Cell Cell

AbstractMorphogenesis is governed by the interplay of molecular signals and mechanical forces across multiple length scales. The last decade has seen tremendous advances in our understanding of the dynamics of protein localization and turnover at sub-cellular length scales, and at the other end of the spectrum, of mechanics at tissue-level length scales. Integrating the two remains a challenge, however, because we lack a detailed understanding of the subcellular patterns of mechanical properties of cells within tissues. Here, in the context of the elongating body axis of a vertebrate embryo, we combine tools from cell biology and physics to demonstrate that individual cell-cell junctions display finely-patterned local mechanical heterogeneity along their length. We show that such local mechanical patterning is essential for the cell movements of convergent extension and is imparted by locally patterned clustering of a classical cadherin. Finally, the patterning of cadherins and thus local mechanics along cell-cell junctions are controlled by Planar Cell Polarity signaling, a key genetic module for CE that is mutated in diverse human birth defects.

scholarly journals Spatial and temporal PCP protein dynamics coordinate cell intercalation during neural tube closure

2018 ◽  
Author(s):  
Mitchell T. Butler ◽  
John B. Wallingford
Keyword(s):  
Neural Tube ◽  
Planar Cell Polarity ◽  
Protein Localization ◽  
Time Lapse ◽  
Neural Tube Closure ◽  
Cell Junctions ◽  
Convergent Extension ◽  
Dynamic Relationships ◽  
Cell Intercalation ◽  
Cell Cell

AbstractPlanar cell polarity (PCP) controls the convergent extension cell movements that drive axis elongation in all vertebrates. Though asymmetric localization of core PCP proteins is central to their function, we currently understand little about PCP protein localization as it relates to the subcellular behaviors that drive convergent extension. Here, we have used high magnification time-lapse imaging to simultaneously monitor cell intercalation behaviors and the localization of the PCP proteins Prickle2 and Vangl2. We observed the expected asymmetric enrichment of PCP proteins, but more interestingly, we also observed tight temporal and spatial correlation of PCP protein enrichment with contractile behavior in cell-cell junctions. These patterns of localization were associated with similar pattern of protein turnover at junctions as assessed by FRAP. In fact, dynamic enrichment of PCP proteins was linked more strongly to junction behavior than to spatial orientation. Finally, recruitment of Prickle2 and Vangl2 to cell-cell junctions was temporally and spatially coordinated with planar polarized oscillations of actomyosin enrichment, and all of these dynamic relationships were disrupted when PCP signaling was manipulated. Together, these results provide a dynamic and quantitative view of PCP protein localization during convergent extension and suggest a complex and intimate link between the dynamic localization of core PCP proteins, actomyosin assembly, and polarized junction shrinking during cell intercalation of the closing vertebrate neural tube.

scholarly journals Spatial and temporal analysis of PCP protein dynamics during neural tube closure

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Mitchell T Butler ◽  
John B Wallingford
Keyword(s):  
Protein Dynamics ◽  
Neural Tube ◽  
Planar Cell Polarity ◽  
Protein Localization ◽  
Temporal Analysis ◽  
Neural Tube Closure ◽  
Cell Junctions ◽  
Convergent Extension ◽  
Turnover Rates ◽  
Cell Intercalation

Planar cell polarity (PCP) controls convergent extension and axis elongation in all vertebrates. Although asymmetric localization of PCP proteins is central to their function, we understand little about PCP protein localization during convergent extension. Here, we use quantitative live imaging to simultaneously monitor cell intercalation behaviors and PCP protein dynamics in the Xenopus laevis neural plate epithelium. We observed asymmetric enrichment of PCP proteins, but more interestingly, we observed tight correlation of PCP protein enrichment with actomyosin-driven contractile behavior of cell-cell junctions. Moreover, we found that the turnover rates of junctional PCP proteins also correlated with the contractile behavior of individual junctions. All these dynamic relationships were disrupted when PCP signaling was manipulated. Together, these results provide a dynamic and quantitative view of PCP protein localization during convergent extension and suggest a complex and intimate link between the dynamic localization of core PCP proteins, actomyosin assembly, and polarized junction shrinking during cell intercalation in the closing vertebrate neural tube.

scholarly journals The cell biology of planar cell polarity

2014 ◽  
Vol 207 (2) ◽  
pp. 171-179 ◽  
Author(s):  
Danelle Devenport
Keyword(s):  
Cell Polarity ◽  
Cell Biology ◽  
Planar Cell Polarity ◽  
Protein Transport ◽  
Protein Localization ◽  
Tissue Level ◽  
Mechanical Forces ◽  
Cellular Polarity ◽  
Asymmetric Partitioning ◽  
Local Cell

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.

scholarly journals Desmosomal Molecules In and Out of Adhering Junctions: Normal and Diseased States of Epidermal, Cardiac and Mesenchymally Derived Cells

2010 ◽  
Vol 2010 ◽  
pp. 1-12 ◽  
Author(s):  
Sebastian Pieperhoff ◽  
Mareike Barth ◽  
Steffen Rickelt ◽  
Werner W. Franke
Keyword(s):  
Cell Biology ◽  
Cell Types ◽  
Cell Junctions ◽  
Surface Molecules ◽  
Transmembrane Glycoprotein ◽  
Current Cell ◽  
Plakophilin 2 ◽  
Definition Of ◽  
Adhering Junctions ◽  
Cell Cell

Current cell biology textbooks mention only two kinds of cell-to-cell adhering junctions coated with the cytoplasmic plaques: the desmosomes (maculae adhaerentes), anchoring intermediate-sized filaments (IFs), and the actin microfilament-anchoring adherens junctions (AJs), including both punctate (puncta adhaerentia) and elongate (fasciae adhaerentes) structures. In addition, however, a series of other junction types has been identified and characterized which contain desmosomal molecules but do not fit the definition of desmosomes. Of these special cell-cell junctions containing desmosomal glycoproteins or proteins we review the composite junctions (areae compositae) connecting the cardiomyocytes of mature mammalian hearts and their importance in relation to human arrhythmogenic cardiomyopathies. We also emphasize the various plakophilin-2-positive plaques in AJs (coniunctiones adhaerentes) connecting proliferatively active mesenchymally-derived cells, including interstitial cells of the heart and several soft tissue tumor cell types. Moreover, desmoplakin has also been recognized as a constituent of the plaques of thecomplexus adhaerentesconnecting certain lymphatic endothelial cells. Finally, we emphasize the occurrence of the desmosomal transmembrane glycoprotein, desmoglein Dsg2, out of the context of any junction as dispersed cell surface molecules in certain types of melanoma cells and melanocytes. This broadening of our knowledge on the diversity of AJ structures indicates that it may still be too premature to close the textbook chapters on cell-cell junctions.

scholarly journals Planar cell polarity: moving from single cells to tissue-scale biology

Development ◽  
2020 ◽  
Vol 147 (24) ◽  
pp. dev186346
Author(s):  
Marek Mlodzik
Keyword(s):  
Cell Polarity ◽  
Cell Biology ◽  
Planar Cell Polarity ◽  
Single Cells ◽  
Field Studies ◽  
Model System ◽  
Convergent Extension ◽  
Organ Function ◽  
Biophysical Studies ◽  
Cell Positioning

ABSTRACTPlanar cell polarity (PCP) reflects cellular orientation within the plane of an epithelium. PCP is crucial during many biological patterning processes and for organ function. It is omnipresent, from convergent-extension mechanisms during early development through to terminal organogenesis, and it regulates many aspects of cell positioning and orientation during tissue morphogenesis, organ development and homeostasis. Suzanne Eaton used the power of Drosophila as a model system to study PCP, but her vision of, and impact on, PCP studies in flies translates to all animal models. As I highlight here, Suzanne's incorporation of quantitative biophysical studies of whole tissues, integrated with the detailed cell biology of PCP phenomena, completely changed how the field studies this intriguing feature. Moreover, Suzanne's impact on ongoing and future PCP studies is fundamental, long-lasting and transformative.

scholarly journals Continuum Theory for Planar Cell Polarity

2021 ◽  
Author(s):  
Mohd. Suhail Rizvi ◽  
Divyoj Singh ◽  
Mohit Kumar Jolly
Keyword(s):  
Cell Membrane ◽  
Cell Polarity ◽  
Protein Interactions ◽  
Planar Cell Polarity ◽  
Protein Localization ◽  
Continuum Theory ◽  
Fruit Fly ◽  
Tissue Level ◽  
Cellular Protein ◽  
Tube Formation

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.

scholarly journals Cell Biology: A Tense but Good Day for Actin at Cell–Cell Junctions

2014 ◽  
Vol 24 (15) ◽  
pp. R688-R690 ◽  
Author(s):  
Stephanie H. Nowotarski ◽  
Mark Peifer
Keyword(s):  
Cell Biology ◽  
Cell Junctions ◽  
Cell Cell

scholarly journals CLAMP/Spef1 regulates planar cell polarity signaling and asymmetric microtubule accumulation in the Xenopus ciliated epithelia

2018 ◽  
Vol 217 (5) ◽  
pp. 1633-1641 ◽  
Author(s):  
Sun K. Kim ◽  
Siwei Zhang ◽  
Michael E. Werner ◽  
Eva J. Brotslaw ◽  
Jennifer W. Mitchell ◽  
...  
Keyword(s):  
Cell Division ◽  
Epithelial Cells ◽  
Cell Signaling ◽  
Cell Polarity ◽  
Planar Cell Polarity ◽  
Protein Localization ◽  
Apical Cell ◽  
Cell Cortex ◽  
Pcp Signaling ◽  
Cell Cell

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.

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