Transmembrane adaptor protein WBP1L regulates CXCR4 signalling and murine haematopoiesis

• Published in: Journal of cellular and molecular medicine Vol. 24; no. 2; pp. 1980 - 1992
• Main Authors: Borna, Simon, Drobek, Ales, Kralova, Jarmila, Glatzova, Daniela, Splichalova, Iva, Fabisik, Matej, Pokorna, Jana, Skopcova, Tereza, Angelisova, Pavla, Kanderova, Veronika, Starkova, Julia, Stanek, Petr, Matveichuk, Orest V., Pavliuchenko, Nataliia, Kwiatkowska, Katarzyna, Protty, Majd B., Tomlinson, Michael G., Alberich‐Jorda, Meritxell, Korinek, Vladimir, Brdicka, Tomas
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.01.2020; John Wiley and Sons Inc
• Subjects: Adaptor Proteins, Signal Transducing - metabolism; Animals; Antibodies; Bone marrow; bone marrow homing; Bone marrow transplantation; Cell lines; Chemokines; Children; Chromatography; Cloning; CXCR4; CXCR4 protein; ETV6; Experiments; Genes; Germ Cells - metabolism; Glycoproteins; Glycoproteins - metabolism; haematopoiesis; haematopoietic stem cell; HEK293 Cells; Hematopoiesis; Hematopoietic Stem Cells - metabolism; Homeostasis; Humans; Immunization; Immunoglobulins; Leukemia; Lipoylation; Localization; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mice, Inbred C57BL; NEDD4 family; OPAL1; Original; Protein Binding; Proteins; Proteomics; Receptors, CXCR4 - metabolism; RNA, Small Interfering - metabolism; RUNX1; Runx1 protein; Signal Transduction; Stem cell transplantation; Translocation; Transplantation; Ubiquitin; Ubiquitin-Protein Ligases - metabolism; Ubiquitination; WBP1L; NEDD4 family; bone marrow homing; CXCR4; WBP1L; OPAL1; bone marrow transplantation; haematopoiesis; haematopoietic stem cell; ETV6; RUNX1
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/jcmm.14895

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.