Ezrin is highly expressed in early thymocytes, but dispensable for T cell development in mice.
BACKGROUND
Ezrin/radixin/moesin (ERM) proteins are highly homologous proteins that function to link cargo molecules to the actin cytoskeleton. Ezrin and moesin are both expressed in mature lymphocytes, where they play overlapping roles in cell signaling and polarity, but their role in lymphoid development has not been explored.


RESULTS
We characterized ERM protein expression in lymphoid tissues and analyzed the requirement for ezrin expression in lymphoid development. In wildtype mice, we found that most cells in the spleen and thymus express both ezrin and moesin, but little radixin. ERM protein expression in the thymus was differentially regulated, such that ezrin expression was highest in immature thymocytes and diminished during T cell development. In contrast, moesin expression was low in early thymocytes and upregulated during T cell development. Mice bearing a germline deletion of ezrin exhibited profound defects in the size and cellularity of the spleen and thymus, abnormal thymic architecture, diminished hematopoiesis, and increased proportions of granulocytic precursors. Further analysis using fetal liver chimeras and thymic transplants showed that ezrin expression is dispensable in hematopoietic and stromal lineages, and that most of the defects in lymphoid development in ezrin(-/-) mice likely arise as a consequence of nutritional stress.


CONCLUSIONS
We conclude that despite high expression in lymphoid precursor cells, ezrin is dispensable for lymphoid development, most likely due to redundancy with moesin.
Shaffer
Meredith H
MH
Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia and University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America.
Huang
Yanping
Y
Corbo
Evann
E
Wu
Gregory F
GF
Velez
Marielena
M
Choi
John K
JK
Saotome
Ichiko
I
Cannon
Judy L
JL
McClatchey
Andrea I
AI
Sperling
Anne I
AI
Maltzman
Jonathan S
JS
Oliver
Paula M
PM
Bhandoola
Avinash
A
Laufer
Terri M
TM
Burkhardt
Janis K
JK
D000818:Animals; D002452:Cell Count; D003598:Cytoskeletal Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006410:Hematopoiesis; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D013997:Time Factors; D015854:Up-Regulation; D000099149:Ezrin
D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D000099149:Ezrin; C071058:moesin; C071776:radixin
Nat Rev Mol Cell Biol. 2002 Aug;3(8):586-99
12154370
J Cell Biol. 2007 Nov 19;179(4):733-46
18025306
J Immunol. 2007 Nov 15;179(10):6403-9
17982027
Eur J Cell Biol. 2003 Aug;82(8):385-400
14533737
Exp Eye Res. 2006 Apr;82(4):720-9
16289046
Immunity. 2001 Nov;15(5):691-701
11728332
Nature. 2003 Jan 2;421(6918):83-7
12511959
EMBO J. 2000 Oct 2;19(19):5123-34
11013215
Nat Immunol. 2004 Mar;5(3):272-9
14758359
FEBS Lett. 1999 Jan 22;443(1):31-6
9928947
Nature. 1959 Dec 5;184(Suppl 23):1809-10
14422530
Nat Genet. 2002 Jul;31(3):320-5
12068294
Immunol Rev. 2002 Nov;189:111-22
12445269
Blood. 2003 Dec 1;102(12):3890-9
12907449
Biochim Biophys Acta. 2008 Sep;1782(9):542-8
18606220
J Cell Sci. 1992 Sep;103 ( Pt 1):131-43
1429901
J Immunol. 2009 Jan 15;182(2):1021-32
19124745
J Biol Chem. 1999 Jan 22;274(4):2315-21
9890997
Nat Genet. 1998 Jul;19(3):282-5
9662405
J Cell Biol. 1998 May 4;141(3):647-62
9566966
J Biol Chem. 2004 Mar 5;279(10):9199-207
14676203
Toxicol Pathol. 2006;34(5):656-65
17067951
Immunity. 2001 Nov;15(5):739-50
11728336
J Biol Chem. 2002 Jan 18;277(3):2321-9
11706008
Biochem Biophys Res Commun. 1991 Jul 15;178(1):16-23
2069555
Immunity. 2001 Nov;15(5):715-28
11728334
Dev Cell. 2004 Jun;6(6):855-64
15177033
J Biol Chem. 1998 Nov 6;273(45):29972-8
9792717
Proc Natl Acad Sci U S A. 1996 Jun 11;93(12):5860-5
8650183