beta-Arrestin Promotes Wnt-induced Low Density Lipoprotein
Receptor-related Protein 6 (Lrp6) Phosphorylation via Increased
Membrane Recruitment of Amer1 Protein

J 2014

beta-Arrestin Promotes Wnt-induced Low Density Lipoprotein Receptor-related Protein 6 (Lrp6) Phosphorylation via Increased Membrane Recruitment of Amer1 Protein

KŘÍŽ, Vítězslav; Vendula POSPÍCHALOVÁ; Jan MAŠEK; Michaela Brita Christina KILANDER; Josef SLAVIK et al.

Základní údaje

Originální název

beta-Arrestin Promotes Wnt-induced Low Density Lipoprotein Receptor-related Protein 6 (Lrp6) Phosphorylation via Increased Membrane Recruitment of Amer1 Protein

Autoři

Vydání

Journal of Biological Chemistry, Rockville, The American Society for Biochemistry and Molecular Biology, 2014, 0021-9258

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10608 Biochemistry and molecular biology

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 4.573

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14310/14:00073566

Organizační jednotka

Přírodovědecká fakulta

Klíčová slova anglicky

CONVERGENT EXTENSION MOVEMENTS; SIGNALING PATHWAYS; IN-VIVO; CATENIN; ACTIVATION; BETA-ARRESTIN-2; DVL; APC; ENDOCYTOSIS; MECHANISM

Štítky

AKR, rivok

Změněno: 4. 10. 2019 15:58, Mgr. Marie Novosadová Šípková, DiS.

Anotace

V originále

beta-Arrestin is a scaffold protein that regulates signal transduction by seven transmembrane-spanning receptors. Among other functions it is also critically required for Wnt/beta-catenin signal transduction. In the present study we provide for the first time a mechanistic basis for the beta-arrestin function in Wnt/beta-catenin signaling. We demonstrate that beta-arrestin is required for efficient Wnt3a-induced Lrp6 phosphorylation, a key event in downstream signaling. beta-Arrestin regulates Lrp6 phosphorylation via a novel interaction with phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P-2)-binding protein Amer1/WTX/Fam123b. Amer1 has been shown very recently to bridge Wnt-induced and Dishevelled-associated PtdIns(4,5)P-2 production to the phosphorylation of Lrp6. Using fluorescence recovery after photobleaching we show here that beta-arrestin is required for the Wnt3a-induced Amer1 membrane dynamics and downstream signaling. Finally, we show that beta-arrestin interacts with PtdIns kinases PI4KII alpha and PIP5KI beta. Importantly, cells lacking beta-arrestin showed higher steady-state levels of the relevant PtdInsP and were unable to increase levels of these PtdInsP in response to Wnt3a. In summary, our data show that beta-arrestins regulate Wnt3a-induced Lrp6 phosphorylation by the regulation of the membrane dynamics of Amer1. We propose that beta-arrestins via their scaffolding function facilitate Amer1 interaction with PtdIns(4,5)P-2, which is produced locally upon Wnt3a stimulation by beta-arrestin- and Dishevelled-associated kinases.

Návaznosti

EE2.3.20.0180, projekt VaV

Název: Spolupráce mezi Masarykovou univerzitou a Karolinska Institutet, Stockholm na poli biomedicíny

EE2.3.30.0009, projekt VaV

Název: Zaměstnáním čerstvých absolventů doktorského studia k vědecké excelenci

GA204/09/0498, projekt VaV

Název: Dynamika proteinů interagujících s Dishevelled a jejich význam pro Wnt signálování

Investor: Grantová agentura ČR, Dynamika proteinů interagujících s Dishevelled a jejich význam pro Wnt signálování

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

Citovat

KŘÍŽ, Vítězslav; Vendula POSPÍCHALOVÁ; Jan MAŠEK; Michaela Brita Christina KILANDER; Josef SLAVIK; Kristina TANNEBERGER; Gunnar SCHULTE; Miroslav MCHALA; Alois KOZUBÍK; Jurgen BEHRENS a Vítězslav BRYJA. beta-Arrestin Promotes Wnt-induced Low Density Lipoprotein Receptor-related Protein 6 (Lrp6) Phosphorylation via Increased Membrane Recruitment of Amer1 Protein. Journal of Biological Chemistry. Rockville: The American Society for Biochemistry and Molecular Biology, 2014, roč. 289, č. 2, s. 1128-1141. ISSN 0021-9258. Dostupné z: https://doi.org/10.1074/jbc.M113.498444.

@article{1173918,
   author = {Kříž, Vítězslav and Pospíchalová, Vendula and Mašek, Jan and Kilander, Michaela Brita Christina and Slavik, Josef and Tanneberger, Kristina and Schulte, Gunnar and Mchala, Miroslav and Kozubík, Alois and Behrens, Jurgen and Bryja, Vítězslav},
   article_location = {Rockville},
   article_number = {2},
   doi = {https://doi.org/10.1074/jbc.M113.498444},
   keywords = {CONVERGENT EXTENSION MOVEMENTS; SIGNALING PATHWAYS; IN-VIVO; CATENIN; ACTIVATION; BETA-ARRESTIN-2; DVL; APC; ENDOCYTOSIS; MECHANISM},
   language = {eng},
   issn = {0021-9258},
   journal = {Journal of Biological Chemistry},
   title = {beta-Arrestin Promotes Wnt-induced Low Density Lipoprotein Receptor-related Protein 6 (Lrp6) Phosphorylation via Increased Membrane Recruitment of Amer1 Protein},
   url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3887180/},
   volume = {289},
   year = {2014}
}

TY  - JOUR
ID  - 1173918
AU  - Kříž, Vítězslav - Pospíchalová, Vendula - Mašek, Jan - Kilander, Michaela Brita Christina - Slavik, Josef - Tanneberger, Kristina - Schulte, Gunnar - Mchala, Miroslav - Kozubík, Alois - Behrens, Jurgen - Bryja, Vítězslav
PY  - 2014
TI  - beta-Arrestin Promotes Wnt-induced Low Density Lipoprotein Receptor-related Protein 6 (Lrp6) Phosphorylation via Increased Membrane Recruitment of Amer1 Protein
JF  - Journal of Biological Chemistry
VL  - 289
IS  - 2
SP  - 1128-1141
EP  - 1128-1141
PB  - The American Society for Biochemistry and Molecular Biology
SN  - 00219258
KW  - CONVERGENT EXTENSION MOVEMENTS
KW  - SIGNALING PATHWAYS
KW  - IN-VIVO
KW  - CATENIN
KW  - ACTIVATION
KW  - BETA-ARRESTIN-2
KW  - DVL
KW  - APC
KW  - ENDOCYTOSIS
KW  - MECHANISM
UR  - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3887180/
N2  - beta-Arrestin is a scaffold protein that regulates signal transduction by seven transmembrane-spanning receptors. Among other functions it is also critically required for Wnt/beta-catenin signal transduction. In the present study we provide for the first time a mechanistic basis for the beta-arrestin function in Wnt/beta-catenin signaling. We demonstrate that beta-arrestin is required for efficient Wnt3a-induced Lrp6 phosphorylation, a key event in downstream signaling. beta-Arrestin regulates Lrp6 phosphorylation via a novel interaction with phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P-2)-binding protein Amer1/WTX/Fam123b. Amer1 has been shown very recently to bridge Wnt-induced and Dishevelled-associated PtdIns(4,5)P-2 production to the phosphorylation of Lrp6. Using fluorescence recovery after photobleaching we show here that beta-arrestin is required for the Wnt3a-induced Amer1 membrane dynamics and downstream signaling. Finally, we show that beta-arrestin interacts with PtdIns kinases PI4KII alpha and PIP5KI beta. Importantly, cells lacking beta-arrestin showed higher steady-state levels of the relevant PtdInsP and were unable to increase levels of these PtdInsP in response to Wnt3a. In summary, our data show that beta-arrestins regulate Wnt3a-induced Lrp6 phosphorylation by the regulation of the membrane dynamics of Amer1. We propose that beta-arrestins via their scaffolding function facilitate Amer1 interaction with PtdIns(4,5)P-2, which is produced locally upon Wnt3a stimulation by beta-arrestin- and Dishevelled-associated kinases.
ER  -

KŘÍŽ, Vítězslav; Vendula POSPÍCHALOVÁ; Jan MAŠEK; Michaela Brita Christina KILANDER; Josef SLAVIK; Kristina TANNEBERGER; Gunnar SCHULTE; Miroslav MCHALA; Alois KOZUBÍK; Jurgen BEHRENS a Vítězslav BRYJA. beta-Arrestin Promotes Wnt-induced Low Density Lipoprotein Receptor-related Protein 6 (Lrp6) Phosphorylation via Increased Membrane Recruitment of Amer1 Protein. \textit{Journal of Biological Chemistry}. Rockville: The American Society for Biochemistry and Molecular Biology, 2014, roč.~289, č.~2, s.~1128-1141. ISSN~0021-9258. Dostupné z: https://doi.org/10.1074/jbc.M113.498444.

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