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

Didier Hodzic*, Jun Wu, Karen Krchma, Andrea Jurisicova, Yonit Tsatskis, Yijie Liu, Peng Ji, Kyunghee Choi*, Helen McNeill*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

AU Nuclear: Pleaseconfirmthatallheadinglevelsarerepresentedcorrectly 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.

Original languageEnglish (US)
Article numbere3001811
JournalPLoS biology
Volume20
Issue number10
DOIs
StatePublished - Oct 2022

ASJC Scopus subject areas

  • General Immunology and Microbiology
  • General Biochemistry, Genetics and Molecular Biology
  • General Neuroscience
  • General Agricultural and Biological Sciences

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