Asymmetry of VANGL2 in migrating lymphocytes as a tool to
monitor activity of the mammalian WNT/planar cell polarity
pathway

J 2015

Asymmetry of VANGL2 in migrating lymphocytes as a tool to monitor activity of the mammalian WNT/planar cell polarity pathway

KAUCKÁ, Markéta, Julian PETERSEN, Pavlína JANOVSKÁ, Tomasz Witold RADASZKIEWICZ, Lucie SMYČKOVÁ et. al.

Basic information

Original name

Asymmetry of VANGL2 in migrating lymphocytes as a tool to monitor activity of the mammalian WNT/planar cell polarity pathway

Authors

KAUCKÁ, Markéta (203 Czech Republic, belonging to the institution), Julian PETERSEN (752 Sweden), Pavlína JANOVSKÁ (203 Czech Republic, belonging to the institution), Tomasz Witold RADASZKIEWICZ (616 Poland, belonging to the institution), Lucie SMYČKOVÁ (203 Czech Republic, belonging to the institution), Avais M DAULAT (250 France), Jean-Paul BORG (250 France), Gunnar SCHULTE (276 Germany, belonging to the institution) and Vítězslav BRYJA (203 Czech Republic, belonging to the institution)

Edition

Journal of Cell Communication and Signaling, 2015, 1478-811X

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

Genetics and molecular biology

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 3.661

RIV identification code

RIV/00216224:14310/15:00080710

Organization unit

Faculty of Science

DOI

http://dx.doi.org/10.1186/s12964-014-0079-1

UT WoS

000348821900001

Keywords in English

Planar cell polarity; Migration; B lymphocyte; VANGL2; Casein kinase 1; MEC1

Abstract

V originále

Background: The WNT/planar-cell-polarity (PCP) pathway is a key regulator of cell polarity and directional cell movements. Core PCP proteins such as Van Gogh-like2 (VANGL2) are evolutionarily highly conserved; however, the mammalian PCP machinery is still poorly understood mainly due to lack of suitable models and quantitative methodology. WNT/PCP has been implicated in many human diseases with the most distinguished positive role in the metastatic process, which accounts for more than 90% of cancer related deaths, and presents therefore an attractive target for pharmacological interventions. However, cellular assays for the assessment of PCP signaling, which would allow a more detailed mechanistic analysis of PCP function and possibly also high throughput screening for chemical compounds targeting mammalian PCP signaling, are still missing. Results: Here we describe a mammalian cell culture model, which correlates B lymphocyte migration of patient-derived MEC1 cells and asymmetric localization of fluorescently-tagged VANGL2. We show by live cell imaging that PCP proteins are polarized in MEC1 cells and that VANGL2 polarization is controlled by the same mechanism as in tissues i.e. it is dependent on casein kinase 1 activity. In addition, destruction of the actin cytoskeleton leads to migratory arrest and cell rounding while VANGL2-EGFP remains polarized suggesting that active PCP signaling visualized by polarized distribution of VANGL2 is a cause for and not a consequence of the asymmetric shape of a migrating cell. Conclusions: The presented imaging-based methodology allows overcoming limitations of earlier approaches to study the mammalian WNT/PCP pathway, which required in vivo models and analysis of complex tissues. Our system investigating PCP-like signaling on a single-cell level thus opens neew possibilities for screening of compounds, which control asymmetric distribution of proteins in the PCP pathway.

Links

GAP301/11/0747, research and development project

Name: Molekulární mechanismy nekanonické Wnt signalizace v leukémii

Investor: Czech Science Foundation

GA13-32990S, research and development project

Name: Posttranslační modifikace receptorů na buněčném povrchu jako určující faktor pro specificitu signálu

Investor: Czech Science Foundation

MSM0021622430, plan (intention)

Name: Funkční a molekulární charakteristiky nádorových a normálních kmenových buněk - identifikace cílů pro nová terapeutika a terapeutické strategie

Investor: Ministry of Education, Youth and Sports of the CR, Functional and molecular characteristics of cancer and normal stem cells - identification of targets for novel therapeutics and therapeutic strategies

NT11217, research and development project

Name: Úloha nekanonické Wnt signalizace v molekulární patogenezi chronické lymfocytární leukémie

Citovat

KAUCKÁ, Markéta, Julian PETERSEN, Pavlína JANOVSKÁ, Tomasz Witold RADASZKIEWICZ, Lucie SMYČKOVÁ, Avais M DAULAT, Jean-Paul BORG, Gunnar SCHULTE and Vítězslav BRYJA. Asymmetry of VANGL2 in migrating lymphocytes as a tool to monitor activity of the mammalian WNT/planar cell polarity pathway. Journal of Cell Communication and Signaling. 2015, vol. 13, January, p. "nestrankovano", 14 pp. ISSN 1478-811X. Available from: https://dx.doi.org/10.1186/s12964-014-0079-1.

@article{1230814,
   author = {Kaucká, Markéta and Petersen, Julian and Janovská, Pavlína and Radaszkiewicz, Tomasz Witold and Smyčková, Lucie and Daulat, Avais M and Borg, JeanandPaul and Schulte, Gunnar and Bryja, Vítězslav},
   article_number = {January},
   doi = {http://dx.doi.org/10.1186/s12964-014-0079-1},
   keywords = {Planar cell polarity; Migration; B lymphocyte; VANGL2; Casein kinase 1; MEC1},
   language = {eng},
   issn = {1478-811X},
   journal = {Journal of Cell Communication and Signaling},
   title = {Asymmetry of VANGL2 in migrating lymphocytes as a tool to monitor activity of the mammalian WNT/planar cell polarity pathway},
   volume = {13},
   year = {2015}
}

TY  - JOUR
ID  - 1230814
AU  - Kaucká, Markéta - Petersen, Julian - Janovská, Pavlína - Radaszkiewicz, Tomasz Witold - Smyčková, Lucie - Daulat, Avais M - Borg, Jean-Paul - Schulte, Gunnar - Bryja, Vítězslav
PY  - 2015
TI  - Asymmetry of VANGL2 in migrating lymphocytes as a tool to monitor activity of the mammalian WNT/planar cell polarity pathway
JF  - Journal of Cell Communication and Signaling
VL  - 13
IS  - January
SP  - "nestrankovano"
EP  - "nestrankovano"
SN  - 1478811X
KW  - Planar cell polarity
KW  - Migration
KW  - B lymphocyte
KW  - VANGL2
KW  - Casein kinase 1
KW  - MEC1
N2  - Background: The WNT/planar-cell-polarity (PCP) pathway is a key regulator of cell polarity and directional cell movements. Core PCP proteins such as Van Gogh-like2 (VANGL2) are evolutionarily highly conserved; however, the mammalian PCP machinery is still poorly understood mainly due to lack of suitable models and quantitative methodology. WNT/PCP has been implicated in many human diseases with the most distinguished positive role in the metastatic process, which accounts for more than 90% of cancer related deaths, and presents therefore an attractive target for pharmacological interventions. However, cellular assays for the assessment of PCP signaling, which would allow a more detailed mechanistic analysis of PCP function and possibly also high throughput screening for chemical compounds targeting mammalian PCP signaling, are still missing. Results: Here we describe a mammalian cell culture model, which correlates B lymphocyte migration of patient-derived MEC1 cells and asymmetric localization of fluorescently-tagged VANGL2. We show by live cell imaging that PCP proteins are polarized in MEC1 cells and that VANGL2 polarization is controlled by the same mechanism as in tissues i.e. it is dependent on casein kinase 1 activity. In addition, destruction of the actin cytoskeleton leads to migratory arrest and cell rounding while VANGL2-EGFP remains polarized suggesting that active PCP signaling visualized by polarized distribution of VANGL2 is a cause for and not a consequence of the asymmetric shape of a migrating cell. Conclusions: The presented imaging-based methodology allows overcoming limitations of earlier approaches to study the mammalian WNT/PCP pathway, which required in vivo models and analysis of complex tissues. Our system investigating PCP-like signaling on a single-cell level thus opens neew possibilities for screening of compounds, which control asymmetric distribution of proteins in the PCP pathway.
ER  -

KAUCKÁ, Markéta, Julian PETERSEN, Pavlína JANOVSKÁ, Tomasz Witold RADASZKIEWICZ, Lucie SMYČKOVÁ, Avais M DAULAT, Jean-Paul BORG, Gunnar SCHULTE and Vítězslav BRYJA. Asymmetry of VANGL2 in migrating lymphocytes as a tool to monitor activity of the mammalian WNT/planar cell polarity pathway. \textit{Journal of Cell Communication and Signaling}. 2015, vol.~13, January, p.~''nestrankovano'', 14 pp. ISSN~1478-811X. Available from: https://dx.doi.org/10.1186/s12964-014-0079-1.

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