scholarly journals Dishevelled stabilization by the ciliopathy protein Rpgrip1l is essential for planar cell polarity

2012 ◽  
Vol 198 (5) ◽  
pp. 927-940 ◽  
Author(s):  
Alexia Mahuzier ◽  
Helori-Mael Gaudé ◽  
Valentina Grampa ◽  
Isabelle Anselme ◽  
Flora Silbermann ◽  
...  
Keyword(s):  
Cell Polarity ◽  
Planar Cell Polarity ◽  
Molecular Mechanisms ◽  
Cultured Cells ◽  
Floor Plate ◽  
Renal Cells ◽  
Polarization Process ◽  
Planar Polarity ◽  
The Core ◽  
Cellular Events

Cilia are at the core of planar polarity cellular events in many systems. However, the molecular mechanisms by which they influence the polarization process are unclear. Here, we identify the function of the ciliopathy protein Rpgrip1l in planar polarity. In the mouse cochlea and in the zebrafish floor plate, Rpgrip1l was required for positioning the basal body along the planar polarity axis. Rpgrip1l was also essential for stabilizing dishevelled at the cilium base in the zebrafish floor plate and in mammalian renal cells. In rescue experiments, we showed that in the zebrafish floor plate the function of Rpgrip1l in planar polarity was mediated by dishevelled stabilization. In cultured cells, Rpgrip1l participated in a complex with inversin and nephrocystin-4, two ciliopathy proteins known to target dishevelled to the proteasome, and, in this complex, Rpgrip1l prevented dishevelled degradation. We thus uncover a ciliopathy protein complex that finely tunes dishevelled levels, thereby modulating planar cell polarity processes.

scholarly journals Multi-scale coordination of planar cell polarity in planarians

2018 ◽  
Author(s):  
Hanh Thi-Kim Vu ◽  
Sarah Mansour ◽  
Michael Kücken ◽  
Corinna Blasse ◽  
Cyril Basquin ◽  
...  
Keyword(s):  
Cell Polarity ◽  
Planar Cell Polarity ◽  
Design Principle ◽  
Cellular Level ◽  
The Body ◽  
Planar Polarity ◽  
Multi Scale ◽  
The Core ◽  
Evolutionarily Conserved ◽  
Polarity Field

SummaryPolarity is a universal design principle of biological systems that manifests at all organizational scales. Although well understood at the cellular level, the mechanisms that coordinate polarity at the tissue or organismal scale remain poorly understood. Here, we make use of the extreme body plan plasticity of planarian flatworms to probe the multi-scale coordination of polarity. Quantitative analysis of ciliary rootlet orientation in the epidermis reveals a global polarization field with head and tail as independent mediators of anteroposterior (A/P) polarization and the body margin influencing mediolateral (M/L) polarization. Mathematical modeling demonstrates that superposition of separate A/P- and M/L-fields can explain the global polarity field and we identify the core planar cell polarity (PCP) and Ft/Ds pathways as their specific mediators. Overall, our study establishes a mechanistic framework for the multi-scale coordination of planar polarity in planarians and establishes the core PCP and Ft/Ds pathways as evolutionarily conserved 2D-polarization module.

scholarly journals The core planar cell polarity gene, Vangl2 , maintains apical‐basal organisation of the corneal epithelium

2017 ◽  
Vol 234 (1) ◽  
pp. 106-119 ◽  
Author(s):  
D. Alessio Panzica ◽  
Amy S. Findlay ◽  
Rianne Ladesteijn ◽  
J. Martin Collinson
Keyword(s):  
Cell Polarity ◽  
Corneal Epithelium ◽  
Planar Cell Polarity ◽  
The Core ◽  
Polarity Gene

scholarly journals Celsr1 and CAMSAP3 differently regulate intercellular and intracellular cilia orientation in oviduct multiciliated cells

2020 ◽  
Author(s):  
Fumiko Matsukawa Usami ◽  
Masaki Arata ◽  
Dongbo Shi ◽  
Sanae Oka ◽  
Yoko Higuchi ◽  
...  
Keyword(s):  
Cell Polarity ◽  
Planar Cell Polarity ◽  
Molecular Mechanisms ◽  
The Other ◽  
Basal Bodies ◽  
Generating Functional ◽  
Tissue Polarity ◽  
Other Hand ◽  
Multiciliated Cells ◽  
Polarity Regulation

SummaryThe molecular mechanisms by which cilia orientation is coordinated within and between multiciliated cells (MCCs) is not fully understood. By observing the orientation of basal bodies (BB) in MCCs of mouse oviducts, here, we show that Celsr1, a planar cell polarity (PCP) factor involved in tissue polarity regulation, is dispensable for determining BB orientation in individual cells, whereas CAMSAP3, a microtubule minus-end regulator, is critical for this process but not for PCP. MCCs exhibit a characteristic BB orientation and microtubule gradient along the tissue axis, and these intracellular polarities were maintained in the cells lacking Celsr1, although the intercellular coordination of the polarities was partly disrupted. On the other hand, CAMSAP3 regulated the assembly of microtubules interconnecting BBs by localizing at the BBs, and its mutation led to disruption of intracellular coordination of BB orientation, but not affecting PCP factor localization. Thus, both Celsr1 and CAMSAP3 are responsible for BB orientation but in distinct ways; and therefore, their cooperation should be critical for generating functional multiciliated tissues.

scholarly journals The core planar cell polarity gene, Vangl2 , directs adult corneal epithelial cell alignment and migration

2016 ◽  
Vol 3 (10) ◽  
pp. 160658 ◽  
Author(s):  
Amy S. Findlay ◽  
D. Alessio Panzica ◽  
Petr Walczysko ◽  
Amy B. Holt ◽  
Deborah J. Henderson ◽  
...  
Keyword(s):  
Cell Migration ◽  
Epithelial Cells ◽  
Cell Polarity ◽  
Corneal Epithelium ◽  
Planar Cell Polarity ◽  
Corneal Epithelial Cell ◽  
Corneal Epithelial Cells ◽  
Corneal Epithelial ◽  
The Core

This study shows that the core planar cell polarity (PCP) genes direct the aligned cell migration in the adult corneal epithelium, a stratified squamous epithelium on the outer surface of the vertebrate eye. Expression of multiple core PCP genes was demonstrated in the adult corneal epithelium. PCP components were manipulated genetically and pharmacologically in human and mouse corneal epithelial cells in vivo and in vitro . Knockdown of VANGL2 reduced the directional component of migration of human corneal epithelial (HCE) cells without affecting speed. It was shown that signalling through PCP mediators, dishevelled, dishevelled-associated activator of morphogenesis and Rho-associated protein kinase directs the alignment of HCE cells by affecting cytoskeletal reorganization. Cells in which VANGL2 was disrupted tended to misalign on grooved surfaces and migrate across, rather than parallel to the grooves. Adult corneal epithelial cells in which Vangl2 had been conditionally deleted showed a reduced rate of wound-healing migration. Conditional deletion of Vangl2 in the mouse corneal epithelium ablated the normal highly stereotyped patterns of centripetal cell migration in vivo from the periphery (limbus) to the centre of the cornea. Corneal opacity owing to chronic wounding is a major cause of degenerative blindness across the world, and this study shows that Vangl2 activity is required for directional corneal epithelial migration.

scholarly journals The Drosophila RNA binding protein Nab2 patterns dendritic arbors and axons via the planar cell polarity pathway

2021 ◽  
Author(s):  
Kenneth H. Moberg ◽  
Edwin B. Corgiat ◽  
Sara List ◽  
J. Christopher Rounds ◽  
Dehong Yu ◽  
...  
Keyword(s):  
Cell Polarity ◽  
Planar Cell Polarity ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Axon Growth ◽  
Planar Cell Polarity Pathway ◽  
Translational Repressor ◽  
The Core ◽  
Dendritic Arbors ◽  
Axon Projection

RNA binding proteins support neurodevelopment by modulating numerous steps in post-transcriptional regulation, including splicing, export, translation, and turnover of mRNAs that can traffic into axons and dendrites. One such RBP is ZC3H14, which is lost in an inherited intellectual disability. The Drosophila melanogaster ZC3H14 ortholog, Nab2, localizes to neuronal nuclei and cytoplasmic ribonucleoprotein granules, and is required for olfactory memory and proper axon projection into brain mushroom bodies. Nab2 can act as a translational repressor in conjunction with the Fragile-X mental retardation protein homolog Fmr1 and shares target RNAs with the Fmr1-interacting RBP Ataxin-2. However, neuronal signaling pathways regulated by Nab2 and their potential roles outside of mushroom body axons remain undefined. Here, we demonstrate that Nab2 restricts branching and projection of larval sensory dendrites via the planar cell polarity pathway, and that this link may provide a conserved mechanism through which Nab2/ZC3H14 modulates projection of both axons and dendrites. Planar cell polarity proteins are enriched in a Nab2-regulated brain proteomic dataset. Complementary genetic data indicate that Nab2 guides dendrite and axon growth through the planar-cell-polarity pathway. Analysis of the core planar cell polarity protein Vang, which is depleted in the Nab2 mutant whole-brain proteome, uncovers selective and dramatic loss of Vang within axon/dendrite-enriched brain neuropil relative to brain regions containing cell bodies. Collectively, these data demonstrate that Nab2 regulates dendritic arbors and axon projection by a planar-cell-polarity-linked mechanism and identify Nab2 as required for accumulation of the core planar cell polarity factor Vang in distal neuronal projections.

scholarly journals Planar cell polarity: the prickle gene acts independently on both the Ds/Ft and the Stan Systems

2017 ◽  
Author(s):  
José Casal ◽  
Beatriz Ibáñez-Jiménez ◽  
Peter A. Lawrence
Keyword(s):  
Cell Polarity ◽  
Planar Cell Polarity ◽  
The Body ◽  
Functional Link ◽  
Molecular Systems ◽  
The Core ◽  
Core Proteins ◽  
Principal Axes ◽  
Essential Components ◽  
Two Systems

ABSTRACTEpithelial cells are polarised within the plane of the epithelium, forming oriented structures whose coordinated and consistent polarity (planar cell polarity, PCP) relates to the principal axes of the body or organ. In Drosophila at least two separate molecular systems generate and interpret intercellular polarity signals: Dachsous/Fat, and the “core” or Stan system. Here we study the prickle gene and its protein products Prickle and Spiny leg. Much research on PCP has focused on the asymmetric localisation of core proteins in the cell and as a result prickle was placed in the heart of the Stan system. Here we ask if this view is correct and how the prickle gene relates to the two systems. We find that prickle can affect, separately, both systems — however, neither Pk nor Sple are essential components of the Ds/Ft or the Stan system, nor do they act as a functional link between the two systems.

scholarly journals Genetically encoded photo-switchable molecular sensors for optoacoustic and super-resolution imaging

2021 ◽  
Author(s):  
Kanuj Mishra ◽  
Juan Pablo Fuenzalida-Werner ◽  
Francesca Pennacchietti ◽  
Robert Janowski ◽  
Andriy Chmyrov ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Fluorescent Protein ◽  
Cultured Cells ◽  
Super Resolution ◽  
Structural Level ◽  
Optoacoustic Imaging ◽  
Molecular Sensors ◽  
The Core ◽  
Resolution Imaging ◽  
G Protein Coupled

AbstractReversibly photo-switchable proteins are essential for many super-resolution fluorescence microscopic and optoacoustic imaging methods. However, they have yet to be used as sensors that measure the distribution of specific analytes at the nanoscale or in the tissues of live animals. Here we constructed the prototype of a photo-switchable Ca2+ sensor based on GCaMP5G that can be switched with 405/488-nm light and describe its molecular mechanisms at the structural level, including the importance of the interaction of the core barrel structure of the fluorescent protein with the Ca2+ receptor moiety. We demonstrate super-resolution imaging of Ca2+ concentration in cultured cells and optoacoustic Ca2+ imaging in implanted tumor cells in mice under controlled Ca2+ conditions. Finally, we show the generalizability of the concept by constructing examples of photo-switching maltose and dopamine sensors based on periplasmatic binding protein and G-protein-coupled receptor-based sensors.

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