Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Disruption of the tumour-associated EMP3 enhances erythroid proliferation and causes the MAM-negative phenotype

Thornton, Nicole ; Karamatic Crew, Vanja ; Tilley, Louise ; Green, Carole A. ; Tay, Chwen Ling ; Griffiths, Rebecca E. ; Singleton, Belinda K. ; Spring, Frances ; Walser, Piers and Alattar, Abdul Ghani LU orcid , et al. (2020) In Nature Communications 11(1).
Abstract

The clinically important MAM blood group antigen is present on haematopoietic cells of all humans except rare MAM-negative individuals. Its molecular basis is unknown. By whole-exome sequencing we identify EMP3, encoding epithelial membrane protein 3 (EMP3), as a candidate gene, then demonstrate inactivating mutations in ten known MAM-negative individuals. We show that EMP3, a purported tumour suppressor in various solid tumours, is expressed in erythroid cells. Disruption of EMP3 by CRISPR/Cas9 gene editing in an immortalised human erythroid cell line (BEL-A2) abolishes MAM expression. We find EMP3 to associate with, and stabilise, CD44 in the plasma membrane. Furthermore, cultured erythroid progenitor cells from MAM-negative... (More)

The clinically important MAM blood group antigen is present on haematopoietic cells of all humans except rare MAM-negative individuals. Its molecular basis is unknown. By whole-exome sequencing we identify EMP3, encoding epithelial membrane protein 3 (EMP3), as a candidate gene, then demonstrate inactivating mutations in ten known MAM-negative individuals. We show that EMP3, a purported tumour suppressor in various solid tumours, is expressed in erythroid cells. Disruption of EMP3 by CRISPR/Cas9 gene editing in an immortalised human erythroid cell line (BEL-A2) abolishes MAM expression. We find EMP3 to associate with, and stabilise, CD44 in the plasma membrane. Furthermore, cultured erythroid progenitor cells from MAM-negative individuals show markedly increased proliferation and higher reticulocyte yields, suggesting an important regulatory role for EMP3 in erythropoiesis and control of cell production. Our data establish MAM as a new blood group system and demonstrate an interaction of EMP3 with the cell surface signalling molecule CD44.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; and (Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Communications
volume
11
issue
1
article number
3569
publisher
Nature Publishing Group
external identifiers
  • scopus:85088100143
  • pmid:32678083
ISSN
2041-1723
DOI
10.1038/s41467-020-17060-4
language
English
LU publication?
yes
id
9874cd2e-af4f-440a-bbc2-0eb070a12b9e
date added to LUP
2020-07-27 12:31:32
date last changed
2024-04-17 12:51:22
@article{9874cd2e-af4f-440a-bbc2-0eb070a12b9e,
  abstract     = {{<p>The clinically important MAM blood group antigen is present on haematopoietic cells of all humans except rare MAM-negative individuals. Its molecular basis is unknown. By whole-exome sequencing we identify EMP3, encoding epithelial membrane protein 3 (EMP3), as a candidate gene, then demonstrate inactivating mutations in ten known MAM-negative individuals. We show that EMP3, a purported tumour suppressor in various solid tumours, is expressed in erythroid cells. Disruption of EMP3 by CRISPR/Cas9 gene editing in an immortalised human erythroid cell line (BEL-A2) abolishes MAM expression. We find EMP3 to associate with, and stabilise, CD44 in the plasma membrane. Furthermore, cultured erythroid progenitor cells from MAM-negative individuals show markedly increased proliferation and higher reticulocyte yields, suggesting an important regulatory role for EMP3 in erythropoiesis and control of cell production. Our data establish MAM as a new blood group system and demonstrate an interaction of EMP3 with the cell surface signalling molecule CD44.</p>}},
  author       = {{Thornton, Nicole and Karamatic Crew, Vanja and Tilley, Louise and Green, Carole A. and Tay, Chwen Ling and Griffiths, Rebecca E. and Singleton, Belinda K. and Spring, Frances and Walser, Piers and Alattar, Abdul Ghani and Jones, Benjamin and Laundy, Rosalind and Storry, Jill R. and Möller, Mattias and Wall, Lorna and Charlewood, Richard and Westhoff, Connie M. and Lomas-Francis, Christine and Yahalom, Vered and Feick, Ute and Seltsam, Axel and Mayer, Beate and Olsson, Martin L. and Anstee, David J.}},
  issn         = {{2041-1723}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Communications}},
  title        = {{Disruption of the tumour-associated EMP3 enhances erythroid proliferation and causes the MAM-negative phenotype}},
  url          = {{http://dx.doi.org/10.1038/s41467-020-17060-4}},
  doi          = {{10.1038/s41467-020-17060-4}},
  volume       = {{11}},
  year         = {{2020}},
}