WW domain binding protein 1-like (WBP1L), also known as outcome predictor of acute leukemia 1 (OPAL1), is a transmembrane adaptor protein, expression of which was shown to correlate with ETV6-RUNX1 translocation and favorable prognosis in childhood leukemia. It has a broad expression pattern in hematopoietic and non-hematopoietic cells. Our previous work described WBP1L as a regulator of CXCR4 signaling and hematopoiesis. Here, we show that hematopoiesis in the mice with Wbp1l germline deletion is dysregulated, already at the level of hematopoietic stem cells and early progenitors. We further demonstrate that thymi of WBP1L-deficient mice are significantly enlarged and contain increased numbers of thymocytes of all subsets. This can potentially be explained by increased generation of multipotent progenitors 4 (MPP4) in the bone marrow, from which the thymus-seeding progenitors are derived. We also observed increases in multiple cell types in the blood. In addition, we show that WBP1L regulates hematopoietic stem cell functionality and leukocyte progenitor proliferation and gene expression during hematopoietic stem and progenitor cell transplantation, which contribute to more efficient engraftment of WBP1L-deficient cells. WBP1L thus emerges as a regulator of hematopoietic stem and progenitor cell function, which controls leukocyte numbers at the steady state and after bone marrow transplantation.

• Keywords
• T cell development, WBP1L, hematopoiesis, hematopoietic stem and progenitor cell transplantation, hematopoietic stem cells, transmembrane adaptor protein,
• MeSH
• Hematopoietic Stem Cells * physiology   MeSH
• Hematopoiesis * MeSH
• Membrane Proteins * genetics   metabolism   MeSH
• Mice, Inbred C57BL MeSH
• Mice, Knockout MeSH
• Mice MeSH
• Leukocyte Count MeSH
• Gene Expression Regulation MeSH
• Thymocytes physiology   MeSH
• Thymus Gland * cytology   physiology   MeSH
• Hematopoietic Stem Cell Transplantation MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Membrane Proteins * MeSH
• Wbp1l protein, mouse MeSH Browser

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.

• Keywords
• CXCR4, ETV6, NEDD4 family, OPAL1, RUNX1, WBP1L, bone marrow homing, bone marrow transplantation, haematopoiesis, haematopoietic stem cell,
• MeSH
• Adaptor Proteins, Signal Transducing metabolism   MeSH
• Glycoproteins metabolism   MeSH
• HEK293 Cells MeSH
• Hematopoietic Stem Cells metabolism   MeSH
• Hematopoiesis * MeSH
• Homeostasis MeSH
• Humans MeSH
• Lipoylation MeSH
• RNA, Small Interfering metabolism   MeSH
• Membrane Proteins genetics   metabolism   MeSH
• Mice, Inbred C57BL MeSH
• Receptors, CXCR4 metabolism   MeSH
• Signal Transduction * MeSH
• Ubiquitination MeSH
• Ubiquitin-Protein Ligases metabolism   MeSH
• Protein Binding MeSH
• Germ Cells metabolism   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Adaptor Proteins, Signal Transducing MeSH
• Glycoproteins MeSH
• RNA, Small Interfering MeSH
• Membrane Proteins MeSH
• Receptors, CXCR4 MeSH
• Ubiquitin-Protein Ligases MeSH
• WBP1L protein, human MeSH Browser
• Wbp1l protein, mouse MeSH Browser