Ezrin Is Highly Expressed in Early Thymocytes, but Dispensable for T Cell Development in Mice

Meredith H Shaffer,Janis K Burkhardt,Ichiko Saotome,Andrea I Mcclatchey,Jonathan S Maltzman,Terri M Laufer,Avinash Bhandoola,Anne I Sperling,Paula M Oliver,Judy L Cannon,Marielena Velez,Gregory F Wu,John K Choi,Yanping Huang,Evann Corbo,Derya Unutmaz

doi:10.1371/journal.pone.0012404

Abstract

BackgroundEzrin/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.Methodology/Principal FindingsWe 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/SignificanceWe conclude that despite high expression in lymphoid precursor cells, ezrin is dispensable for lymphoid development, most likely due to redundancy with moesin.

Highlights

The ERM proteins ezrin, radixin and moesin tether transmembrane and cytoplasmic molecules to actin filaments at the cell cortex in a regulated manner
Depending on the expression patterns of ERM proteins or the independent roles of these molecules, individual ERM proteins may play an important role in T cell development. We show both ezrin and moesin are expressed in the thymus, but that ezrin levels are highest in immature DN and DP thymocytes, while moesin levels are highest in more mature SP thymocytes
It has become clear that ERM proteins play an important role in the function of mature lymphocytes

Summary

Introduction

The ERM proteins ezrin, radixin and moesin tether transmembrane and cytoplasmic molecules to actin filaments at the cell cortex in a regulated manner. In T cells, ERM proteins are important for numerous functions including maintenance of microvilli, organization of proximal-distal T cell polarity, regulation of CD95-induced cell death, and promotion of TCR-induced signaling events leading to cytokine production [5,6,7,8,9,10,11,12,13]. Because of their high sequence similarity, ezrin, radixin, and moesin are usually thought to be functionally redundant. 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

Methods

Results

Conclusion