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 differen...

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Autores principales:	Alexander Mattebo, Taha Sen, Maria Jassinskaja, Kristýna Pimková, Isabel Prieto González-Albo, Abdul Ghani Alattar, Ramprasad Ramakrishnan, Stefan Lang, Marcus Järås, Jenny Hansson, Shamit Soneji, Sofie Singbrant, Emile van den Akker, Johan Flygare
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5dc977dcbe104bb4b3fa8157f49bbc12
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spelling	oai:doaj.org-article:5dc977dcbe104bb4b3fa8157f49bbc122021-12-02T18:49:25ZYippee like 4 (Ypel4) is essential for normal mouse red blood cell membrane integrity10.1038/s41598-021-95291-12045-2322https://doaj.org/article/5dc977dcbe104bb4b3fa8157f49bbc122021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95291-1https://doaj.org/toc/2045-2322Abstract 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.Alexander MatteboTaha SenMaria JassinskajaKristýna PimkováIsabel Prieto González-AlboAbdul Ghani AlattarRamprasad RamakrishnanStefan LangMarcus JäråsJenny HanssonShamit SonejiSofie SingbrantEmile van den AkkerJohan FlygareNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Alexander Mattebo Taha Sen Maria Jassinskaja Kristýna Pimková Isabel Prieto González-Albo Abdul Ghani Alattar Ramprasad Ramakrishnan Stefan Lang Marcus Järås Jenny Hansson Shamit Soneji Sofie Singbrant Emile van den Akker Johan Flygare Yippee like 4 (Ypel4) is essential for normal mouse red blood cell membrane integrity
description	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.
format	article
author	Alexander Mattebo Taha Sen Maria Jassinskaja Kristýna Pimková Isabel Prieto González-Albo Abdul Ghani Alattar Ramprasad Ramakrishnan Stefan Lang Marcus Järås Jenny Hansson Shamit Soneji Sofie Singbrant Emile van den Akker Johan Flygare
author_facet	Alexander Mattebo Taha Sen Maria Jassinskaja Kristýna Pimková Isabel Prieto González-Albo Abdul Ghani Alattar Ramprasad Ramakrishnan Stefan Lang Marcus Järås Jenny Hansson Shamit Soneji Sofie Singbrant Emile van den Akker Johan Flygare
author_sort	Alexander Mattebo
title	Yippee like 4 (Ypel4) is essential for normal mouse red blood cell membrane integrity
title_short	Yippee like 4 (Ypel4) is essential for normal mouse red blood cell membrane integrity
title_full	Yippee like 4 (Ypel4) is essential for normal mouse red blood cell membrane integrity
title_fullStr	Yippee like 4 (Ypel4) is essential for normal mouse red blood cell membrane integrity
title_full_unstemmed	Yippee like 4 (Ypel4) is essential for normal mouse red blood cell membrane integrity
title_sort	yippee like 4 (ypel4) is essential for normal mouse red blood cell membrane integrity
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/5dc977dcbe104bb4b3fa8157f49bbc12
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Yippee like 4 (Ypel4) is essential for normal mouse red blood cell membrane integrity

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