Transmembrane adaptor protein WBP1L regulates CXCR4 signalling and murine haematopoiesis

被引:8
作者
Borna, Simon [1 ,2 ]
Drobek, Ales [1 ]
Kralova, Jarmila [1 ]
Glatzova, Daniela [1 ,2 ,3 ]
Splichalova, Iva [4 ]
Fabisik, Matej [1 ,2 ]
Pokorna, Jana [1 ]
Skopcova, Tereza [1 ]
Angelisova, Pavla [1 ]
Kanderova, Veronika [5 ,6 ]
Starkova, Julia [5 ,6 ]
Stanek, Petr [7 ]
Matveichuk, Orest, V [8 ]
Pavliuchenko, Nataliia [1 ,2 ]
Kwiatkowska, Katarzyna [8 ]
Protty, Majd B. [9 ]
Tomlinson, Michael G. [10 ]
Alberich-Jorda, Meritxell [11 ]
Korinek, Vladimir [12 ]
Brdicka, Tomas [1 ]
机构
[1] Czech Acad Sci, Inst Mol Genet, Lab Leukocyte Signaling, Prague, Czech Republic
[2] Charles Univ Prague, Fac Sci, Prague, Czech Republic
[3] Czech Acad Sci, J Heyrovsky Inst Phys Chem, Dept Biophys Chem, Prague, Czech Republic
[4] Czech Acad Sci, Inst Mol Genet, Lab Immunobiol, Prague, Czech Republic
[5] Charles Univ Prague, Fac Med 2, Childhood Leukaemia Invest Prague, Prague, Czech Republic
[6] Charles Univ Prague, Fac Med 2, Dept Pediat Hematol & Oncol, Prague, Czech Republic
[7] Charles Univ Prague, Fac Med 2, Prague, Czech Republic
[8] Nencki Inst Expt Biol, Lab Mol Membrane Biol, Warsaw, Poland
[9] Univ Birmingham, Inst Biomed Res, Birmingham, W Midlands, England
[10] Univ Birmingham, Sch Biosci, Birmingham, W Midlands, England
[11] Czech Acad Sci, Inst Mol Genet, Lab Hematooncol, Prague, Czech Republic
[12] Czech Acad Sci, Inst Mol Genet, Lab Cell & Dev Biol, Prague, Czech Republic
基金
欧盟地平线“2020”; 英国医学研究理事会;
关键词
bone marrow homing; bone marrow transplantation; CXCR4; ETV6; haematopoiesis; haematopoietic stem cell; NEDD4; family; OPAL1; RUNX1; WBP1L; WHIM-SYNDROME; GENE; EXPRESSION; LEUKEMIA; UBIQUITIN; ETV6; TEL/ETV6; TEL;
D O I
10.1111/jcmm.14895
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
WW domain binding protein 1-like (WBP1L), also known as outcome predictor of acute leukaemia 1 (OPAL1), is a transmembrane adaptor protein, expression of which correlates with ETV6-RUNX1 (t(12;21)(p13;q22)) translocation and favourable prognosis in childhood leukaemia. It has a broad expression pattern in haematopoietic and in non-haematopoietic cells. However, its physiological function has been unknown. Here, we show that WBP1L negatively regulates signalling through a critical chemokine receptor CXCR4 in multiple leucocyte subsets and cell lines. We also show that WBP1L interacts with NEDD4-family ubiquitin ligases and regulates CXCR4 ubiquitination and expression. Moreover, analysis of Wbp1l-deficient mice revealed alterations in B cell development and enhanced efficiency of bone marrow cell transplantation. Collectively, our data show that WBP1L is a novel regulator of CXCR4 signalling and haematopoiesis.
引用
收藏
页码:1980 / 1992
页数:13
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