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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Published in:PLoS biology 2022-10, Vol.20 (10), p.e3001811-e3001811
Main Authors: Hodzic, Didier, Wu, Jun, Krchma, Karen, Jurisicova, Andrea, Tsatskis, Yonit, Liu, Yijie, Ji, Peng, Choi, Kyunghee, McNeill, Helen
Format: Article
Language:English
Subjects:
Anemia
Animals
Apoptosis
Biology and Life Sciences
Blood
Bone marrow
Cell Nucleus - metabolism
Cell research
Enucleation
Erythroblasts
Erythroblasts - metabolism
Erythropoiesis
Erythropoiesis - genetics
Fertility
Genetic aspects
Granulocytes
Hemoglobin
Maturation
Membrane proteins
Membrane Proteins - genetics
Membrane Proteins - metabolism
Membranes
Mice
Mice, Knockout
Neonates
Nuclear Envelope
Peripheral blood
Phenotypes
Properties
Proteins
Research and Analysis Methods
Rodents
Short Reports
Spleen
Splenomegaly
Stem cells
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cited_by cdi_FETCH-LOGICAL-c554t-f8d17c71463fd620f9df7ea56dbb6c92a9d95d1a71686119a21e7eba619771373
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creator Hodzic, Didier
Wu, Jun
Krchma, Karen
Jurisicova, Andrea
Tsatskis, Yonit
Liu, Yijie
Ji, Peng
Choi, Kyunghee
McNeill, Helen
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.
doi_str_mv 10.1371/journal.pbio.3001811
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source Publicly Available Content Database; PubMed Central
subjects Anemia
Animals
Apoptosis
Biology and Life Sciences
Blood
Bone marrow
Cell Nucleus - metabolism
Cell research
Enucleation
Erythroblasts
Erythroblasts - metabolism
Erythropoiesis
Erythropoiesis - genetics
Fertility
Genetic aspects
Granulocytes
Hemoglobin
Maturation
Membrane proteins
Membrane Proteins - genetics
Membrane Proteins - metabolism
Membranes
Mice
Mice, Knockout
Neonates
Nuclear Envelope
Peripheral blood
Phenotypes
Properties
Proteins
Research and Analysis Methods
Rodents
Short Reports
Spleen
Splenomegaly
Stem cells
title The inner nuclear membrane protein NEMP1 supports nuclear envelope openings and enucleation of erythroblasts
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