Open AccessTransmembrane adaptor protein WBP1L regulates CXCR4 signalling and murine haematopoiesis
Author(s) -
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.,
AlberichJorda Meritxell,
Korinek Vladimir,
Brdicka Tomas
Publication year - 2020
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.14895
Subject(s) - biology , haematopoiesis , ubiquitin , ww domain , microbiology and biotechnology , transmembrane protein , signal transducing adaptor protein , regulator , cxcr4 , chemokine receptor , nedd4 , ubiquitin ligase , runx1 , lymphopoiesis , signal transduction , cancer research , receptor , chemokine , immunology , immune system , stem cell , genetics , gene
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.