Nuclear VANGL2 Inhibits Lactogenic Differentiation DOI Open Access

Stefany Rubio,

Rut Molinuevo, Natalia Sanz‐Gómez

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Дек. 8, 2023

ABSTRACT Planar cell polarity (PCP) proteins coordinate tissue morphogenesis by governing patterning and polarity. Asymmetrically localized on the plasma membrane of cells, PCP are also trafficked endocytosis, suggesting they may have intracellular functions that dependent or independent their extracellular role, but whether these extend to transcriptional control remains unknown. Here, we show nuclear localization transmembrane, protein, VANGL2, in undifferentiated, not differentiated, HC11 which serve as a model for mammary lactogenic differentiation. Loss Vangl2 function results upregulation pathways related STAT5 signaling. We identify DNA binding sites signal use CUT&RUN demonstrate direct VANGL2 specific motifs, including one Stat5a promoter. Knockdown (KD) cells primary organoids , Ccnd1 Csn2 larger acini organoids, precocious differentiation; phenotypes rescued overexpression ΔNLS . Together, advance paradigm whereby keeping programs differentiation check.

Язык: Английский

Spatially resolved proteomics of the Arabidopsis stomatal lineage identifies polarity complexes for cell divisions and stomatal pores DOI Creative Commons
Eva‐Sophie Wallner, Andrea Mair, Dominik Handler

и другие.

Developmental Cell, Год журнала: 2024, Номер 59(9), С. 1096 - 1109.e5

Опубликована: Март 21, 2024

Cell polarity is used to guide asymmetric divisions and create morphologically diverse cells. We find that two oppositely oriented cortical domains present during the in Arabidopsis stomatal lineage are reconfigured into polar marking ventral (pore-forming) outward-facing of maturing guard Proteins define these opposing were as baits miniTurboID-based proximity labeling. Among differentially enriched proteins, we kinases, putative microtubule-interacting SOSEKIs with their effector ANGUSTIFOLIA. Using AI-facilitated protein structure prediction models, identify potential protein-protein interaction interfaces among them. Functional localization analyses OPL2 its partners suggest a positive mitotic microtubules role cytokinesis. This combination proteomics structural modeling live-cell imaging provides insights how rewired different cell types cell-cycle stages.

Язык: Английский

Процитировано

9

Structural basis of human VANGL-PRICKLE interaction DOI Creative Commons
Yanyi Song,

Shuyi Jian,

Junlin Teng

и другие.

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Янв. 3, 2025

Planar cell polarity (PCP) is an evolutionarily conserved process for development and morphogenesis in metazoans. The well-organized pattern cells established by the asymmetric distribution of two core protein complexes on opposite sides membrane. Van Gogh-like (VANGL)-PRICKLE (PK) pair one these key regulators; however, their structural information detailed functions have been unclear. Here, we present five cryo-electron microscopy structures human VANGL1, VANGL2, with PK1 at resolutions 2.2–3.0 Å. Through biochemical imaging experiments, decipher molecular details VANGL-PK interaction. Furthermore, reveal that can target VANGL-containing intracellular vesicles to peripheral These findings provide a solid foundation understand explicit interaction between VANGL PK while opening new avenues subsequent studies PCP pathway. authors VANGL2 PK1, unveiling underpinnings paving way future investigations into planar pathway

Язык: Английский

Процитировано

0

Small Extracellular Vesicles Promote Axon Outgrowth by Engaging the Wnt-Planar Cell Polarity Pathway DOI Creative Commons
Samar Ahmad, Tania Christova,

Melanie Pye

и другие.

Cells, Год журнала: 2025, Номер 14(1), С. 56 - 56

Опубликована: Янв. 6, 2025

In neurons, the acquisition of a polarized morphology is achieved upon outgrowth single axon from one several neurites. Small extracellular vesicles (sEVs), such as exosomes, diverse sources are known to promote neurite and thus may have therapeutic potential. However, effect fibroblast-derived exosomes on elongation in neurons central nervous system under growth-permissive conditions remains unclear. Here, we show that sEVs neuronal mouse primary embryonic cortical neurons. Mechanistically, demonstrate sEV-induced increase requires endogenous Wnts core PCP components including Prickle, Vangl, Frizzled, Dishevelled. We internalized by colocalize with Wnt7b, induce relocalization Vangl2 distal during outgrowth. contrast, derived or astrocytes do not outgrowth, while activated inhibit elongation. Thus, our data reveal through Wnt-PCP pathway manner dependent Wnts.

Язык: Английский

Процитировано

0

Molecular and cellular processes underlying Unverricht-Lundborg disease—prospects for early interventions and a cure DOI Creative Commons
Eva Žerovnik

Exploration of neuroscience, Год журнала: 2024, Номер 3(4), С. 295 - 308

Опубликована: Июль 18, 2024

A short overview of the main features progressive myoclonus epilepsies (PMEs), such as Lafora disease (LD), neuronal ceroid lipofuscinoses (NCLs), and epilepsy with ragged-red fibers (MERRF) is given. The stress this review paper put on one PME’s, Unverricht-Lundborg (ULD)—EPM1, which caused by mutations in human cystatin B gene (stefin an alternative protein’s name). However, different other genes/proteins were found mutated patients presenting EPM1-like symptoms. By understanding their function pathophysiological roles, further insights into underlying processes EPM1 can be obtained. On a broader scale, common mechanisms exist between ULD, LD NCLs, as, reactive glia, synaptic remodeling, hyperexcitability, impairements lysosomal/endocytosis system, cytoskeletal functions, mitochondria. Oxidative also common. molecular cellular processes, early interventions, better therapies eventually, using modern stem cell, editing or replacement methods, cure expected.

Язык: Английский

Процитировано

2

Nuclear VANGL2 Inhibits Lactogenic Differentiation DOI Creative Commons

Stefany Rubio,

Rut Molinuevo, Natalia Sanz‐Gómez

и другие.

Cells, Год журнала: 2024, Номер 13(3), С. 222 - 222

Опубликована: Янв. 25, 2024

Planar cell polarity (PCP) proteins coordinate tissue morphogenesis by governing patterning and polarity. Asymmetrically localized on the plasma membrane of cells, transmembrane PCP are trafficked endocytosis, suggesting they may have intracellular functions that dependent or independent their extracellular role, but whether these extend to transcriptional control remains unknown. Here, we show nuclear localization transmembrane, protein, VANGL2, in HCC1569 breast cancer line, undifferentiated, not differentiated, HC11 cells serve as a model for mammary lactogenic differentiation. The loss Vangl2 function results upregulation pathways related STAT5 signaling. We identify DNA binding sites signal use CUT&RUN demonstrate recruitment VANGL2 specific motifs, including one Stat5a promoter. Knockdown (KD) primary organoids Stat5a, Ccnd1 Csn2, larger acini organoids, precocious differentiation; phenotypes rescued overexpression Vangl2, Vangl2ΔNLS. Together, advance paradigm whereby keeping programs differentiation check.

Язык: Английский

Процитировано

0

The Planar Cell Polarity Protein Fat1 in Sertoli Cell Function DOI Creative Commons

Tiao Bu,

Lingling Wang, Xiaolong Wu

и другие.

Endocrinology, Год журнала: 2024, Номер 165(6)

Опубликована: Март 30, 2024

Abstract Fat (FAT atypical cadherin) and Dchs (Dachsous cadherin–related protein) in adjacent Sertoli:Sertoli, Sertoli:spermatid, spermatid:spermatid interfaces create an important intercellular bridge whose adhesive function is turn supported by Fjx1, a nonreceptor Ser/Thr protein kinase. This concept derived from earlier studies of Drosophila, which has been confirmed this reports as well. Herein, we use the approach knockdown Fat1 RNAi using primary cultures Sertoli cells that mimicked blood–testis barrier (BTB) vivo, series coherent experiments including functional assays to monitor cell tight junction (TJ) permeability vitro TJ integrity assay assess role testis. It was shown planar polarity (PCP) affected through its modulation actin microtubule cytoskeletal function, altering their polymerization activity Fat1/Fjx1 complex. Furthermore, intimately associated with β-catenin α-N-catenin, well Prickle 1 Vangl1/Prickle complex, another PCP core support interactions confer PCP. In summary, these findings notion Fat:Dchs Vangl2:Fzd bridges are tightly basal ES/TJ structural proteins stabilize at interface sustain spermatogenesis.

Язык: Английский

Процитировано

0

Differential Sensitivity of Midline Patterning to Mitosis during and after Primitive Streak Extension DOI
Zhiling Zhao, Rieko Asai, Takashi Mikawa

и другие.

Опубликована: Окт. 26, 2024

Abstract Background Midline establishment is a fundamental process during early embryogenesis for Bilaterians . patterning in nonamniotes can occur without mitosis, through Planar Cell Polarity (PCP) signaling. By contrast, amniotes utilize both cell proliferation and PCP signaling midline landmark, the primitive streak (PS). This study examined their roles at post PS-extension. Results In contrast to PS extension stages, embryos under mitotic arrest PS-extension preserved notochord (NC) Hensen’s node (HN)/PS regression judged by morphology marker genes, although they became shorter, laterality was lost. Remarkably, no or background level of expression detected majority core components NC-HN-PS area except robustly prickle-1 Morpholino knockdown Prickle-1 showed little influence on patterning, suppressed embryonic growth. Lastly, associated with arrest-induced size reduction, tissue cells displayed hypertrophy. Conclusion Thus, has identified least two distinct mitosis sensitivity phases pattering: One that requires PCP, other arrest-resistant stages.

Язык: Английский

Процитировано

0

Exosomes promote axon outgrowth by engaging the Wnt-Planar Cell Polarity pathway DOI Open Access
Samar Ahmad,

Melanie Pye,

Masahiro Narimatsu

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Окт. 28, 2023

In neurons, the acquisition of a polarized morphology is achieved upon outgrowth single axon from one several neurites. Exosomes or small extracellular vesicles (sEVs) diverse sources are known to promote neurite and thus may have therapeutic potential. However, effect fibroblast-derived exosomes on elongation in neurons central nervous system under growth permissive conditions remains unclear. Here, we show that sEVs neuronal mouse primary embryonic cortical neurons. Mechanistically, demonstrate sEV-induced increase requires endogenous Wnts core PCP components including Prickle, Vangl, Frizzled Dishevelled. We internalized by colocalize with Wnt7b induce relocalization Vangl2 distal during outgrowth. contrast, derived astrocytes do not outgrowth, while activated inhibit elongation. Thus, our data reveals through Wnt-PCP pathway manner dependent Wnts.

Язык: Английский

Процитировано

0

Spatially resolved proteomics of the stomatal lineage: polarity complexes for cell divisions and stomatal pores DOI Creative Commons
Eva‐Sophie Wallner, Andrea Mair, Dominik Handler

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Ноя. 3, 2023

Abstract Cell polarity is used to guide asymmetric divisions and create morphologically diverse cells. We find that two oppositely oriented cortical domains present during the in Arabidopsis stomatal lineage are reconfigured into polar marking ventral (pore-forming) outward facing of maturing guard Proteins define these opposing were as baits miniTurboID-based proximity labeling. Among differentially enriched proteins we kinases, putative microtubule-interacting proteins, SOSEKIs with their effector ANGUSTIFOLIA, using AI-facilitated protein structure prediction models, identify potential interaction interfaces. Functional localization analysis OPL2 its newly discovered partners suggest a positive mitotic microtubules role cytokinesis. This combination cutting-edge proteomics structural modeling live cell imaging provides insights how rewired different types cycle stages.

Язык: Английский

Процитировано

0

Nuclear VANGL2 Inhibits Lactogenic Differentiation DOI Open Access

Stefany Rubio,

Rut Molinuevo, Natalia Sanz‐Gómez

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Дек. 8, 2023

ABSTRACT Planar cell polarity (PCP) proteins coordinate tissue morphogenesis by governing patterning and polarity. Asymmetrically localized on the plasma membrane of cells, PCP are also trafficked endocytosis, suggesting they may have intracellular functions that dependent or independent their extracellular role, but whether these extend to transcriptional control remains unknown. Here, we show nuclear localization transmembrane, protein, VANGL2, in undifferentiated, not differentiated, HC11 which serve as a model for mammary lactogenic differentiation. Loss Vangl2 function results upregulation pathways related STAT5 signaling. We identify DNA binding sites signal use CUT&RUN demonstrate direct VANGL2 specific motifs, including one Stat5a promoter. Knockdown (KD) cells primary organoids , Ccnd1 Csn2 larger acini organoids, precocious differentiation; phenotypes rescued overexpression ΔNLS . Together, advance paradigm whereby keeping programs differentiation check.

Язык: Английский

Процитировано

0