Ezrin and Moesin Are Required for Efficient T Cell Adhesion and Homing to Lymphoid Organs

Chen, Emily J. H.; Shaffer, Meredith H.; Williamson, Edward K.; Huang, Yanping; Burkhardt, Janis K.
February 2013
PLoS ONE;Feb2013, Vol. 8 Issue 2, p1
Academic Journal
T cell trafficking between the blood and lymphoid organs is a complex, multistep process that requires several highly dynamic and coordinated changes in cyto-architecture. Members of the ezrin, radixin and moesin (ERM) family of actin-binding proteins have been implicated in several aspects of this process, but studies have yielded conflicting results. Using mice with a conditional deletion of ezrin in CD4+ cells and moesin-specific siRNA, we generated T cells lacking ERM proteins, and investigated the effect on specific events required for T cell trafficking. ERM-deficient T cells migrated normally in multiple in vitro and in vivo assays, and could undergo efficient diapedesis in vitro. However, these cells were impaired in their ability to adhere to the β1 integrin ligand fibronectin, and to polarize appropriately in response to fibronectin and VCAM-1 binding. This defect was specific for β1 integrins, as adhesion and polarization in response to ICAM-1 were normal. In vivo, ERM-deficient T cells showed defects in homing to lymphoid organs. Taken together, these results show that ERM proteins are largely dispensable for T cell chemotaxis, but are important for β1 integrin function and homing to lymphoid organs.


Related Articles

  • Rodzina biaÅ‚ek ERM (ezrin/radixin/moesin) - rola i znaczenie w procesach polaryzacji, adhezji i mobilnoÅ›ci komórkowej. Hałoń, Agnieszka; Donizy, Piotr // Advances in Hygiene & Experimental Medicine / Postepy Higieny i ;2012, Vol. 66, p158 

    Ezrin, radixin and moesin, forming the ERM protein family, act as molecular crosslinkers between actin filaments and proteins anchored in the cell membrane. By participating in a complex intracellular network of signal transduction pathways, ERM proteins play a key role in the regulation of...

  • The Arp2/3 complex nucleates actin filament branches from the sides of pre-existing filaments. Amann, Kurt J.; Pollard, Thomas D. // Nature Cell Biology;Mar2001, Vol. 3 Issue 3, p306 

    Regulated assembly of actin-filament networks provides the mechanical force that pushes forward the leading edge of motile eukaryotic cells[SUP1] and intracellular pathogenic bacteria[SUP2] and viruses[SUP3]. When activated by binding to actin filaments and to the WA domain of...

  • PKCθ Regulates T Cell Motility via Ezrin-Radixin-Moesin Localization to the Uropod. Cannon, Judy L.; Asperti-Boursin, Francois; Letendre, Kenneth A.; Brown, Ivy K.; Korzekwa, Katy E.; Blaine, Kelly M.; Oruganti, Sreenivasa R.; Sperling, Anne I.; Moses, Melanie E. // PLoS ONE;Nov2013, Vol. 8 Issue 11, p1 

    Cell motility is a fundamental process crucial for function in many cell types, including T cells. T cell motility is critical for T cell-mediated immune responses, including initiation, activation, and effector function. While many extracellular receptors and cytoskeletal regulators have been...

  • 17β-Estradiol Enhances Breast Cancer Cell Motility and Invasion via Extra-Nuclear Activation of Actin-Binding Protein Ezrin. Shuhui Zheng; Jinghe Huang; Kewen Zhou; Chengxi Zhang; Qiuling Xiang; Zhi Tan; Tinghuai Wang; Xiaodong Fu // PLoS ONE;2011, Vol. 6 Issue 7, p1 

    Estrogen promotes breast cancer metastasis. However, the detailed mechanism remains largely unknown. The actin binding protein ezrin is a key component in tumor metastasis and its over-expression is positively correlated to the poor outcome of breast cancer. In this study, we investigate the...

  • Enhanced Integrin a4b1–Mediated Adhesion Contributes to a Mobilization Defect of Endothelial Progenitor Cells in Diabetes. Abplanalp, Wesley T.; Conklin, Daniel J.; Cantor, Joseph M.; Ginsberg, Mark H.; Wysoczynski, Marcin; Bhatnagar, Aruni; O'Toole, Timothy E. // Diabetes;Nov2016, Vol. 65 Issue 11, p3505 

    Diabetes is associated with a deficit of circulating endothelial progenitor cells (EPCs), which has been attributed to their defective mobilization from the bone marrow. The basis for this mobilization defect is not completely understood, and we sought to determine if hyperglycemic conditions...

  • The Novel Role for Lyn in Integrin Signaling in Human Disease. Tomkowicz, Brian; Ptasznik, Andrzej // Current Signal Transduction Therapy;Jan2009, Vol. 4 Issue 1, p59 

    Cell movement and adhesion serve critical roles in a wide variety of physiological situations, and when dysregulated can contribute to the pathogenesis of many diseases. Recently, Lyn kinase has emerged as a crucial regulator of 'inside-out' integrin signaling in hematopoietic cells, that when...

  • CLASPs link focal-adhesion-associated microtubule capture to localized exocytosis and adhesion site turnover. Stehbens, Samantha J.; Paszek, Matthew; Pemble, Hayley; Ettinger, Andreas; Gierke, Sarah; Wittmann, Torsten // Nature Cell Biology;Jun2014, Vol. 16 Issue 6, p561 

    Turnover of integrin-based focal adhesions (FAs) with the extracellular matrix (ECM) is essential for coordinated cell movement. In collectively migrating human keratinocytes, FAs assemble near the leading edge, grow and mature as a result of contractile forces and disassemble underneath the...

  • ILK, PINCH and parvin: the tIPP of integrin signalling. Legate, Kyle R.; Montañez, Eloi; Kudlacek, Oliver; Fässler, Reinhard // Nature Reviews Molecular Cell Biology;Jan2006, Vol. 7 Issue 1, p20 

    The ternary complex of integrin-linked kinase (ILK), PINCH and parvin functions as a signalling platform for integrins by interfacing with the actin cytoskeleton and many diverse signalling pathways. All these proteins have synergistic functions at focal adhesions, but recent work has indicated...

  • E-Cadherin Suppression Directs Cytoskeletal Rearrangement and Intraepithelial Tumor Cell Migration in 3D Human Skin Equivalents. Alt-Holland, Addy; Shamis, Yulia; Riley, Kathleen N; DesRochers, Teresa M; Fusenig, Norbert E; Herman, Ira M; Garlick, Jonathan A // Journal of Investigative Dermatology;Oct2008, Vol. 128 Issue 10, p2498 

    The link between loss of cell–cell adhesion, the activation of cell migration, and the behavior of intraepithelial (IE) tumor cells during the early stages of skin cancer progression is not well understood. The current study characterized the migratory behavior of a squamous cell...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics