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.

Základní údaje

Originální název

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

Autoři

KAUCKÁ, Markéta (203 Česká republika, domácí), Julian PETERSEN (752 Švédsko), Pavlína JANOVSKÁ (203 Česká republika, domácí), Tomasz Witold RADASZKIEWICZ (616 Polsko, domácí), Lucie SMYČKOVÁ (203 Česká republika, domácí), Avais M DAULAT (250 Francie), Jean-Paul BORG (250 Francie), Gunnar SCHULTE (276 Německo, domácí) a Vítězslav BRYJA (203 Česká republika, domácí)

Vydání

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

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

Genetika a molekulární biologie

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 3.661

Kód RIV

RIV/00216224:14310/15:00080710

Organizační jednotka

Přírodovědecká fakulta

DOI

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

UT WoS

000348821900001

Klíčová slova anglicky

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

Štítky

AKR, rivok

Změněno: 28. 4. 2016 14:02, Ing. Andrea Mikešková

Anotace

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.

Návaznosti

GAP301/11/0747, projekt VaV

Název: Molekulární mechanismy nekanonické Wnt signalizace v leukémii

Investor: Grantová agentura ČR, Molekulární mechanismy nekanonické Wnt signalizace v leukémii

GA13-32990S, projekt VaV

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

Investor: Grantová agentura ČR, Posttranslační modifikace receptorů na buněčném povrchu jako určující faktor pro specificitu signálu

MSM0021622430, záměr

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

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Funkční a molekulární charakteristiky nádorových a normálních kmenových buněk - identifikace cílů pro nová terapeutika a terapeutické strategie

NT11217, projekt VaV

Název: 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 a 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, roč. 13, January, s. "nestrankovano", 14 s. ISSN 1478-811X. Dostupné z: 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 a 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, roč.~13, January, s.~''nestrankovano'', 14 s. ISSN~1478-811X. Dostupné z: https://dx.doi.org/10.1186/s12964-014-0079-1.

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