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The inner nuclear membrane protein NEMP1 supports nuclear envelope openings and enucleation of erythroblasts

Nuclear envelope membrane proteins (NEMPs) are a conserved family of nuclear envelope (NE) proteins that reside within the inner nuclear membrane (INM). Even though Nemp1 knockout (KO) mice are overtly normal, they display a pronounced splenomegaly. This phenotype and recent reports describing a req...

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Autores principales: Hodzic, Didier, Wu, Jun, Krchma, Karen, Jurisicova, Andrea, Tsatskis, Yonit, Liu, Yijie, Ji, Peng, Choi, Kyunghee, McNeill, Helen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9595564/
https://www.ncbi.nlm.nih.gov/pubmed/36215313
http://dx.doi.org/10.1371/journal.pbio.3001811
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author Hodzic, Didier
Wu, Jun
Krchma, Karen
Jurisicova, Andrea
Tsatskis, Yonit
Liu, Yijie
Ji, Peng
Choi, Kyunghee
McNeill, Helen
author_facet Hodzic, Didier
Wu, Jun
Krchma, Karen
Jurisicova, Andrea
Tsatskis, Yonit
Liu, Yijie
Ji, Peng
Choi, Kyunghee
McNeill, Helen
author_sort Hodzic, Didier
collection PubMed
description Nuclear envelope membrane proteins (NEMPs) are a conserved family of nuclear envelope (NE) proteins that reside within the inner nuclear membrane (INM). Even though Nemp1 knockout (KO) mice are overtly normal, they display a pronounced splenomegaly. This phenotype and recent reports describing a requirement for NE openings during erythroblasts terminal maturation led us to examine a potential role for Nemp1 in erythropoiesis. Here, we report that Nemp1 KO mice show peripheral blood defects, anemia in neonates, ineffective erythropoiesis, splenomegaly, and stress erythropoiesis. The erythroid lineage of Nemp1 KO mice is overrepresented until the pronounced apoptosis of polychromatophilic erythroblasts. We show that NEMP1 localizes to the NE of erythroblasts and their progenitors. Mechanistically, we discovered that NEMP1 accumulates into aggregates that localize near or at the edge of NE openings and Nemp1 deficiency leads to a marked decrease of both NE openings and ensuing enucleation. Together, our results for the first time demonstrate that NEMP1 is essential for NE openings and erythropoietic maturation in vivo and provide the first mouse model of defective erythropoiesis directly linked to the loss of an INM protein.
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spelling pubmed-95955642022-10-26 The inner nuclear membrane protein NEMP1 supports nuclear envelope openings and enucleation of erythroblasts Hodzic, Didier Wu, Jun Krchma, Karen Jurisicova, Andrea Tsatskis, Yonit Liu, Yijie Ji, Peng Choi, Kyunghee McNeill, Helen PLoS Biol Short Reports Nuclear envelope membrane proteins (NEMPs) are a conserved family of nuclear envelope (NE) proteins that reside within the inner nuclear membrane (INM). Even though Nemp1 knockout (KO) mice are overtly normal, they display a pronounced splenomegaly. This phenotype and recent reports describing a requirement for NE openings during erythroblasts terminal maturation led us to examine a potential role for Nemp1 in erythropoiesis. Here, we report that Nemp1 KO mice show peripheral blood defects, anemia in neonates, ineffective erythropoiesis, splenomegaly, and stress erythropoiesis. The erythroid lineage of Nemp1 KO mice is overrepresented until the pronounced apoptosis of polychromatophilic erythroblasts. We show that NEMP1 localizes to the NE of erythroblasts and their progenitors. Mechanistically, we discovered that NEMP1 accumulates into aggregates that localize near or at the edge of NE openings and Nemp1 deficiency leads to a marked decrease of both NE openings and ensuing enucleation. Together, our results for the first time demonstrate that NEMP1 is essential for NE openings and erythropoietic maturation in vivo and provide the first mouse model of defective erythropoiesis directly linked to the loss of an INM protein. Public Library of Science 2022-10-10 /pmc/articles/PMC9595564/ /pubmed/36215313 http://dx.doi.org/10.1371/journal.pbio.3001811 Text en © 2022 Hodzic et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Short Reports
Hodzic, Didier
Wu, Jun
Krchma, Karen
Jurisicova, Andrea
Tsatskis, Yonit
Liu, Yijie
Ji, Peng
Choi, Kyunghee
McNeill, Helen
The inner nuclear membrane protein NEMP1 supports nuclear envelope openings and enucleation of erythroblasts
title The inner nuclear membrane protein NEMP1 supports nuclear envelope openings and enucleation of erythroblasts
title_full The inner nuclear membrane protein NEMP1 supports nuclear envelope openings and enucleation of erythroblasts
title_fullStr The inner nuclear membrane protein NEMP1 supports nuclear envelope openings and enucleation of erythroblasts
title_full_unstemmed The inner nuclear membrane protein NEMP1 supports nuclear envelope openings and enucleation of erythroblasts
title_short The inner nuclear membrane protein NEMP1 supports nuclear envelope openings and enucleation of erythroblasts
title_sort inner nuclear membrane protein nemp1 supports nuclear envelope openings and enucleation of erythroblasts
topic Short Reports
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9595564/
https://www.ncbi.nlm.nih.gov/pubmed/36215313
http://dx.doi.org/10.1371/journal.pbio.3001811
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