scholarly journals Ancestral roles of atypical cadherins in planar cell polarity

2020 ◽  
Vol 117 (32) ◽  
pp. 19310-19320
Author(s):  
Maria Brooun ◽  
Alexander Klimovich ◽  
Mikhail Bashkurov ◽  
Bret J. Pearson ◽  
Robert E. Steele ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Cell Polarity ◽  
Planar Cell Polarity ◽  
Sister Group ◽  
The Body ◽  
Cell Alignment ◽  
Actin Organization ◽  
Tissue Organization ◽  
Ancestral Function ◽  
Local Cell

Fat, Fat-like, and Dachsous family cadherins are giant proteins that regulate planar cell polarity (PCP) and cell adhesion in bilaterians. Their evolutionary origin can be traced back to prebilaterian species, but their ancestral function(s) are unknown. We identified Fat-like and Dachsous cadherins inHydra, a member of phylum Cnidaria a sister group of bilaterian. We foundHydradoes not possess a true Fat homolog, but has homologs of Fat-like (HyFatl) and Dachsous (HyDs) that localize at the apical membrane of ectodermal epithelial cells and are planar polarized perpendicular to the oral–aboral axis of the animal. Using a knockdown approach we found that HyFatl is involved in local cell alignment and cell–cell adhesion, and that reduction of HyFatl leads to defects in tissue organization in the body column. Overexpression and knockdown experiments indicate that the intracellular domain (ICD) of HyFatl affects actin organization through proline-rich repeats. Thus, planar polarization of Fat-like and Dachsous cadherins has ancient, prebilaterian origins, and Fat-like cadherins have ancient roles in cell adhesion, spindle orientation, and tissue organization.

scholarly journals Ancestral role of Fat-like cadherins in planar cell polarity

2019 ◽  
Author(s):  
Maria Brooun ◽  
Alexander Klimovich ◽  
Mikhail Bashkurov ◽  
Bret J. Pearson ◽  
Robert E. Steele ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Cell Polarity ◽  
Planar Cell Polarity ◽  
Radial Symmetry ◽  
Global Alignment ◽  
Cell Alignment ◽  
Tissue Organization ◽  
Ancestral Function ◽  
Simple Body ◽  
Epithelial Layers

ABSTRACTFat family cadherins are enormous proteins that regulate planar cell polarity (PCP) and cell adhesion in bilaterian animals. Their evolutionary origin can be traced back to prebilaterian species, but their ancestral function(s) are unknown. We identified Fat-like and Dachsous cadherins in Hydra, a member of the early-diverging metazoan phylum Cnidaria. Hydra has a simple body plan with only two epithelial layers and radial symmetry. We find that Hydra homologues of Fat-like (HyFat) and Dachsous (HyDs) co-localize at the apico-lateral membrane of ectodermal epithelial cells. Remarkably, HyFat is planar polarized perpendicular to the oral-aboral axis of the animal. Using knockdown approaches we found that HyFat is involved in the regulation of local cell alignment, but is dispensable for the global alignment of ectodermal myonemes along the oral-aboral axis. The intracellular domain (ICD) of HyFat is involved in the morphogenesis of ectodermal myonemes. Thus, Fat family cadherins have ancient, prebilaterian functions in cell adhesion, tissue organization and planar polarity.

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 Planar cell polarity signalling regulates cell adhesion properties in progenitors of the zebrafish laterality organ

Development ◽  
2010 ◽  
Vol 137 (20) ◽  
pp. 3459-3468 ◽  
Author(s):  
P. Oteiza ◽  
M. Koppen ◽  
M. Krieg ◽  
E. Pulgar ◽  
C. Farias ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Cell Polarity ◽  
Planar Cell Polarity ◽  
Adhesion Properties ◽  
Planar Cell Polarity Signalling

scholarly journals Wnt-11 and Fz7 reduce cell adhesion in convergent extension by sequestration of PAPC and C-cadherin

2012 ◽  
Vol 198 (4) ◽  
pp. 695-709 ◽  
Author(s):  
Bianca Kraft ◽  
Corinna D. Berger ◽  
Veronika Wallkamm ◽  
Herbert Steinbeisser ◽  
Doris Wedlich
Keyword(s):  
Cell Adhesion ◽  
Xenopus Laevis ◽  
Cell Polarity ◽  
Cell Sorting ◽  
Planar Cell Polarity ◽  
Convergent Extension ◽  
Membrane Stabilization ◽  
Dynamic Modulation ◽  
Interaction Domains ◽  
Shape Changes

Wnt-11/planar cell polarity signaling polarizes mesodermal cells undergoing convergent extension during Xenopus laevis gastrulation. These shape changes associated with lateral intercalation behavior require a dynamic modulation of cell adhesion. In this paper, we report that Wnt-11/frizzled-7 (Fz7) controls cell adhesion by forming separate adhesion-modulating complexes (AMCs) with the paraxial protocadherin (PAPC; denoted as AMCP) and C-cadherin (denoted as AMCC) via distinct Fz7 interaction domains. When PAPC was part of a Wnt-11–Fz7 complex, its Dynamin1- and clathrin-dependent internalization was blocked. This membrane stabilization of AMCP (Fz7/PAPC) by Wnt-11 prevented C-cadherin clustering, resulting in reduced cell adhesion and modified cell sorting activity. Importantly, Wnt-11 did not influence C-cadherin internalization; instead, it promoted the formation of AMCC (Fz7/Cadherin), which competed with cis-dimerization of C-cadherin. Because PAPC and C-cadherin did not directly interact and did not form a joint complex with Fz7, we suggest that Wnt-11 triggers the formation of two distinct complexes, AMCC and AMCP, that act in parallel to reduce cell adhesion by hampering lateral clustering of C-cadherin.

scholarly journals Thymosin β4 is essential for adherens junction stability and epidermal planar cell polarity

Development ◽  
2020 ◽  
Vol 147 (23) ◽  
pp. dev193425
Author(s):  
Krishnanand Padmanabhan ◽  
Hanna Grobe ◽  
Jonathan Cohen ◽  
Arad Soffer ◽  
Adnan Mahly ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Cell Polarity ◽  
Actin Polymerization ◽  
Planar Cell Polarity ◽  
Adherens Junction ◽  
Actin Binding ◽  
Thymosin Β4 ◽  
Eyelid Closure

ABSTRACTPlanar cell polarity (PCP) is essential for tissue morphogenesis and homeostasis; however, the mechanisms that orchestrate the cell shape and packing dynamics required to establish PCP are poorly understood. Here, we identified a major role for the globular (G)-actin-binding protein thymosin-β4 (TMSB4X) in PCP establishment and cell adhesion in the developing epidermis. Depletion of Tmsb4x in mouse embryos hindered eyelid closure and hair-follicle angling owing to PCP defects. Tmsb4x depletion did not preclude epidermal cell adhesion in vivo or in vitro; however, it resulted in abnormal structural organization and stability of adherens junction (AJ) due to defects in filamentous (F)-actin and G-actin distribution. In cultured keratinocytes, TMSB4X depletion increased the perijunctional G/F-actin ratio and decreased G-actin incorporation into junctional actin networks, but it did not change the overall actin expression level or cellular F-actin content. A pharmacological treatment that increased the G/F-actin ratio and decreased actin polymerization mimicked the effects of Tmsb4x depletion on both AJs and PCP. Our results provide insights into the regulation of the actin pool and its involvement in AJ function and PCP establishment.

The cell polarity PTK7 receptor acts as a modulator of the chemotherapeutic response in acute myeloid leukemia and impairs clinical outcome

Blood ◽  
2010 ◽  
Vol 116 (13) ◽  
pp. 2315-2323 ◽  
Author(s):  
Thomas Prebet ◽  
Anne-Catherine Lhoumeau ◽  
Christine Arnoulet ◽  
Anaïs Aulas ◽  
Sylvie Marchetto ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Cell Polarity ◽  
Myeloid Leukemia ◽  
Planar Cell Polarity ◽  
Bone Marrow Cells ◽  
Tyrosine Kinase Receptor ◽  
Epithelial Tissue ◽  
Tissue Organization ◽  
Acute Myeloid

Abstract The pseudo tyrosine kinase receptor 7 (PTK7) is an orphan tyrosine kinase receptor assigned to the planar cell polarity pathway. It plays a major role during embryogenesis and epithelial tissue organization. Here we found that PTK7 is also expressed in normal myeloid progenitors and CD34+ CD38− bone marrow cells in humans. We performed an immunophenotyping screen on more than 300 patients treated for hematologic malignancies. We demonstrated that PTK7 is expressed in acute myeloid leukemia (AML) and is mostly assigned to granulocytic lineage differentiation. Patients with PTK7-positive AML are more resistant to anthracycline-based frontline therapy with a significantly reduced leukemia-free survival in a multivariate analysis model. In vitro, expression of PTK7 in cultured leukemia cells promotes cell migration, cell survival, and resistance to anthracycline-induced apoptosis. The intracellular region of PTK7 is required for these effects. Furthermore, we efficiently sensitized primary AML blasts to anthracycline-mediated cell death using a recombinant soluble PTK7-Fc protein. We conclude that PTK7 is a planar cell polarity component expressed in the myeloid progenitor compartment that conveys promigratory and antiapoptotic signals into the cell and that represents an independent prognosis factor of survival in patients treated with induction chemotherapy.

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