Dataset Information

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.

SUBMITTER: Mattebo A

PROVIDER: S-EPMC8342551 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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

Mattebo Alexander A Sen Taha T Jassinskaja Maria M Pimková Kristýna K Prieto González-Albo Isabel I Alattar Abdul Ghani AG Ramakrishnan Ramprasad R Lang Stefan S Järås Marcus M Hansson Jenny J Soneji Shamit S Singbrant Sofie S van den Akker Emile E Flygare Johan J

Scientific reports 20210805 1

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- ...[more]

PMID: 34354145

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Project description:An understanding of the basic pathophysiological mechanisms of neonatal diseases necessitates detailed knowledge about the wide range of complications in the circulating fetal RBCs. Recent publications on adult red blood cells (RBCs) provide evidence that RBCs carry an active nitric oxide synthase (NOS3) enzyme and contribute to vascular functioning and integrity via their active nitric oxide synthesis. The aim of this study was to determine the effect of maternal smoking on the phenotypical appearance and functionality of fetal RBCs, based on morphological and molecular studies. We looked for possible links between vascular dysfunction and NOS3 expression and activation and its regulation by arginase (ARG1). Significant morphological and functional differences were found between fetal RBCs isolated from the arterial cord blood of neonates born to nonsmoking (RBC-NS, n = 62) and heavy-smoking (RBC-S, n = 51) mothers. Morphological variations were quantified by Advanced Cell Classifier, microscopy-based intelligent analysis software. To investigate the relevance of the newly suggested "erythrocrine" function in fetal RBCs, we measured the levels of NOS3 and its phosphorylation in parallel with the level of ARG1, as one of the major influencers of NOS3 dimerization, by fluorescence-activated cell sorting. Fetal RBCs, even the "healthy-looking" biconcave-shaped type, exhibited impaired NOS3 activation in the RBC-S population, which was paralleled with elevated ARG1 level, thus suggesting an increased redox burden. Our molecular data indicate that maternal smoking can exert marked effects on the circulating fetal RBCs, which could have a consequence on the outcome of in utero development. We hypothesize that any endothelial dysfunction altering NO production/bioavailability can be sensed by circulating fetal RBCs. Hence, we are putting forward the idea that neonatal RBC could serve as a real-time sensor for not only monitoring RBC-linked anomalies but also predicting the overall status of the vascular microenvironment.

Dataset Information

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

Publications

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

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