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.

2nd Faculty of Medicine Charles University Prague Czech Republic

CLIP Childhood Leukaemia Investigation Prague and Department of Pediatric Hematology and Oncology 2nd Faculty of Medicine Charles University Prague Czech Republic

Department of Biophysical Chemistry J Heyrovsky Institute of Physical Chemistry of the Czech Academy of Sciences Prague Czech Republic

Faculty of Science Charles University Prague Czech Republic

Institute of Biomedical Research University of Birmingham Birmingham UK

Laboratory of Cell and Developmental Biology Institute of Molecular Genetics of the Czech Academy of Sciences Prague Czech Republic

Laboratory of Hematooncology Institute of Molecular Genetics of the Czech Academy of Sciences Prague Czech Republic

Laboratory of Immunobiology Institute of Molecular Genetics of the Czech Academy of Sciences Prague Czech Republic

Laboratory of Leukocyte Signaling Institute of Molecular Genetics of the Czech Academy of Sciences Prague Czech Republic

Laboratory of Molecular Membrane Biology Nencki Institute of Experimental Biology Warsaw Poland

School of Biosciences University of Birmingham Birmingham UK

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WBP1L regulates hematopoietic stem cell function and T cell development

Bardet-Biedl Syndrome ciliopathy is linked to altered hematopoiesis and dysregulated self-tolerance