Yippee like 4 (Ypel4) is essential for normal mouse red blood cell membrane integrity

Abstract

The YPEL family genes are highly conserved across a diverse range of eukaryotic organisms and thus potentially involved in essential cellular processes. Ypel4, one of five YPEL family gene orthologs in mouse and human, is highly and specifically expressed in late terminal erythroid differentiation (TED). In this study, we investigated the role of Ypel4 in murine erythropoiesis, providing for the first time an in-depth description of a Ypel4-null phenotype in vivo. We demonstrated that the Ypel4-null mice displayed a secondary polycythemia with macro- and reticulocytosis. While lack of Ypel4 did not affect steady-state TED in the bone marrow or spleen, the anemia-recovering capacity of Ypel4-null cells was diminished. Furthermore, Ypel4-null red blood cells (RBC) were cleared from the circulation at an increased rate, demonstrating an intrinsic defect of RBCs. Scanning electron micrographs revealed an ovalocytic morphology of Ypel4-null RBCs and functional testing confirmed reduced deformability. Even though Band 3 protein levels were shown to be reduced in Ypel4-null RBC membranes, we could not find support for a physical interaction between YPEL4 and the Band 3 protein. In conclusion, our findings provide crucial insights into the role of Ypel4 in preserving normal red cell membrane integrity.

The mRNA and miRNA profiles of goat bronchial epithelial cells stimulated by Pasteurella multocida strains of serotype A and D

“…TLRs are protective immune sentries that are known for their role in innate immunity, detecting and defending against microbial pathogens ( Lim & Staudt, 2013 ; Brennan & Gilmore, 2018 ). YPEL2 and YPEL4 annotated to this pathway are both members of the YPEL (yippee-like) gene family, which are highly conserved across a diverse range of eukaryotic organisms ( Mattebo et al, 2021 ). However, there are few studies on YPEL2 .…”

Dynamic proximity interaction profiling suggests that YPEL2 is involved in cellular stress surveillance

“…Lee et al, 2017;W. Li et al, 2022;Liang et al, 2010;Mattebo et al, 2021;Oki et al, 2016;Tan et al, 2015;Tuttle et al, 2012;J. Zhang et al, 2016) studies on YPEL2 are limited.…”

“…This high evolutionary conservation among YPEL proteins implies that YPELs are critically involved in various cellular processes. Indeed, experimental studies suggest that the YPEL proteins, including YPEL2, participate in cellular proliferation, mitochondrial function, morphology, mobility, differentiation, senescence, and death (Aerts et al, 2006a ; Blanco‐Sanchez et al, 2020 ; Farlie et al, 2001 ; Garcıá et al, 2019 ; Hosono et al, 2004 , 2010 ; Jun et al, 2007 ; K. D. Kelley et al, 2010 ; J. H. Kim et al, 2020 ; Kong et al, 2018 ; J. Y. Lee et al, 2017 ; W. Li et al, 2022 ; Liang et al, 2010 ; Mattebo et al, 2021 ; Oki et al, 2016 ; Sullivan, 2001 ; Tan et al, 2015 ; Tuttle et al, 2012 ; J. Zhang et al, 2016 ). Moreover, deregulated expression of YPEL genes could be associated with, or contribute to, the initiation/development of various disorders, malignancies, and resistance to therapies (Blanco‐Sanchez et al, 2020 ; Hosono et al, 2010 ; S. Li et al, 2019 ; W. Li et al, 2022 ; Mattebo et al, 2021 ; Tuttle et al, 2011 ; Vysotskiy et al, 2021 ; L. Wang et al, 2022 ; Wu, 2018 ).…”

“…Li et al, 2019;W. Li et al, 2022;Mattebo et al, 2021;Tuttle et al, 2011;Vysotskiy et al, 2021;L. Wang et al, 2022;Wu, 2018).…”

Impacts of vitrification on the transcriptome of human ovarian tissue in patients with gynecological cancer

“…Some studies have shown that human primordial follicles survive freezing and thawing quite efficiently with survival rates of more than 80%, whereas only 20-40% of the follicles survive after transplantation because of revascularization (Kristensen et al, 2018;Gavish et al, 2018), which is considered the biggest limitation to OTC. ETV7, YPEL4, and CXCR4 have been identified as important transcription factors involved in hematopoiesis (Wu et al, 2020;Mattebo et al, 2021;Kawaguchi et al, 2019). ETV7 and YPEL4 were upregulated, and CXCR4 mRNA was downregulated in human ovary tissues after vitrification, which may be a stress response to cryopreservation damage.…”