Lymphocyte Egress Signal Sphingosine-1-phosphate Promotes ERM-guided, Bleb-based Migration

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2021 Mar 25

PMID 33764397

Citations 9

Authors

Tanner F Robertson

Pragati Chengappa

Daniela Gomez Atria

Christine F Wu

Lyndsay Avery

Nathan H Roy

Ivan Maillard

Ryan J Petrie

Janis K Burkhardt

Affiliations

Soon will be listed here.

Abstract

Ezrin, radixin, and moesin (ERM) family proteins regulate cytoskeletal responses by tethering the plasma membrane to the underlying actin cortex. Mutations in ERM proteins lead to severe combined immunodeficiency, but the function of these proteins in T cells remains poorly defined. Using mice in which T cells lack all ERM proteins, we demonstrate a selective role for these proteins in facilitating S1P-dependent egress from lymphoid organs. ERM-deficient T cells display defective S1P-induced migration in vitro, despite normal responses to standard protein chemokines. Analysis of these defects revealed that S1P promotes a fundamentally different mode of migration than chemokines, characterized by intracellular pressurization and bleb-based motility. ERM proteins facilitate this process, controlling directional migration by limiting blebbing to the leading edge. We propose that the distinct modes of motility induced by S1P and chemokines are specialized to allow T cell migration across lymphatic barriers and through tissue stroma, respectively.

Citing Articles

Splenic fibroblasts control marginal zone B cell movement and function via two distinct Notch2-dependent regulatory programs.

Allman A, Gaudette B, Kelly S, Alouche N, Carrington L, Perkey E Immunity. 2024; 58(1):143-161.e8.

PMID: 39731910 PMC: 11735314. DOI: 10.1016/j.immuni.2024.12.003.

Blebology: principles of bleb-based migration.

Garcia-Arcos J, Jha A, Waterman C, Piel M Trends Cell Biol. 2024; 34(10):838-853.

PMID: 38538441 PMC: 11424778. DOI: 10.1016/j.tcb.2024.02.009.

S1PR1 inhibition induces proapoptotic signaling in T cells and limits humoral responses within lymph nodes.

Dixit D, Hallisey V, Zhu E, Okuniewska M, Cadwell K, Chipuk J J Clin Invest. 2024; 134(4).

PMID: 38194271 PMC: 10869180. DOI: 10.1172/JCI174984.

Non-muscle myosin II and the plasticity of 3D cell migration.

Cowan J, Duggan J, Hewitt B, Petrie R Front Cell Dev Biol. 2022; 10:1047256.

PMID: 36438570 PMC: 9691290. DOI: 10.3389/fcell.2022.1047256.

Advancements on the Multifaceted Roles of Sphingolipids in Hematological Malignancies.

Raza Y, Atallah J, Luberto C Int J Mol Sci. 2022; 23(21).

PMID: 36361536 PMC: 9654982. DOI: 10.3390/ijms232112745.

References

Forster R, Schubel A, Breitfeld D, Kremmer E, Renner-Muller I, Wolf E . CCR7 coordinates the primary immune response by establishing functional microenvironments in secondary lymphoid organs. Cell. 1999; 99(1):23-33. DOI: 10.1016/s0092-8674(00)80059-8. View

Grigorova I, Schwab S, Phan T, Pham T, Okada T, Cyster J . Cortical sinus probing, S1P1-dependent entry and flow-based capture of egressing T cells. Nat Immunol. 2008; 10(1):58-65. PMC: 2710451. DOI: 10.1038/ni.1682. View

Nomachi A, Yoshinaga M, Liu J, Kanchanawong P, Tohyama K, Thumkeo D . Moesin controls clathrin-mediated S1PR1 internalization in T cells. PLoS One. 2013; 8(12):e82590. PMC: 3865155. DOI: 10.1371/journal.pone.0082590. View

Liu Y, Belkina N, Park C, Nambiar R, Loughhead S, Patino-Lopez G . Constitutively active ezrin increases membrane tension, slows migration, and impedes endothelial transmigration of lymphocytes in vivo in mice. Blood. 2011; 119(2):445-53. PMC: 3257010. DOI: 10.1182/blood-2011-07-368860. View

Lyons A, Parish C . Are murine marginal-zone macrophages the splenic white pulp analog of high endothelial venules?. Eur J Immunol. 1995; 25(11):3165-72. DOI: 10.1002/eji.1830251127. View

Petrie R, Koo H . Direct measurement of intracellular pressure. Curr Protoc Cell Biol. 2014; 63:12.9.1-9. PMC: 4075330. DOI: 10.1002/0471143030.cb1209s63. View

Vrzalikova K, Ibrahim M, Vockerodt M, Perry T, Margielewska S, Lupino L . S1PR1 drives a feedforward signalling loop to regulate BATF3 and the transcriptional programme of Hodgkin lymphoma cells. Leukemia. 2017; 32(1):214-223. PMC: 5737877. DOI: 10.1038/leu.2017.275. View

Lagresle-Peyrou C, Luce S, Ouchani F, Soheili T, Sadek H, Chouteau M . X-linked primary immunodeficiency associated with hemizygous mutations in the moesin (MSN) gene. J Allergy Clin Immunol. 2016; 138(6):1681-1689.e8. DOI: 10.1016/j.jaci.2016.04.032. View

Tooley A, Gilden J, Jacobelli J, Beemiller P, Trimble W, Kinoshita M . Amoeboid T lymphocytes require the septin cytoskeleton for cortical integrity and persistent motility. Nat Cell Biol. 2008; 11(1):17-26. PMC: 3777658. DOI: 10.1038/ncb1808. View

10.

Parameswaran N, Matsui K, Gupta N . Conformational switching in ezrin regulates morphological and cytoskeletal changes required for B cell chemotaxis. J Immunol. 2011; 186(7):4088-97. PMC: 3106416. DOI: 10.4049/jimmunol.1001139. View

11.

Chen E, Shaffer M, Williamson E, Huang Y, Burkhardt J . Ezrin and moesin are required for efficient T cell adhesion and homing to lymphoid organs. PLoS One. 2013; 8(2):e52368. PMC: 3585410. DOI: 10.1371/journal.pone.0052368. View

12.

Hayashi K, Yonemura S, Matsui T, Tsukita S . Immunofluorescence detection of ezrin/radixin/moesin (ERM) proteins with their carboxyl-terminal threonine phosphorylated in cultured cells and tissues. J Cell Sci. 1999; 112 ( Pt 8):1149-58. DOI: 10.1242/jcs.112.8.1149. View

13.

Dejana E, Orsenigo F, Molendini C, Baluk P, McDonald D . Organization and signaling of endothelial cell-to-cell junctions in various regions of the blood and lymphatic vascular trees. Cell Tissue Res. 2008; 335(1):17-25. PMC: 4422058. DOI: 10.1007/s00441-008-0694-5. View

14.

Allende M, Dreier J, Mandala S, Proia R . Expression of the sphingosine 1-phosphate receptor, S1P1, on T-cells controls thymic emigration. J Biol Chem. 2004; 279(15):15396-401. DOI: 10.1074/jbc.M314291200. View

15.

Grayson M, Hotchkiss R, Karl I, Holtzman M, Chaplin D . Intravital microscopy comparing T lymphocyte trafficking to the spleen and the mesenteric lymph node. Am J Physiol Heart Circ Physiol. 2003; 284(6):H2213-26. DOI: 10.1152/ajpheart.00999.2002. View

16.

Jacobelli J, Friedman R, Conti M, Lennon-Dumenil A, Piel M, Sorensen C . Confinement-optimized three-dimensional T cell amoeboid motility is modulated via myosin IIA-regulated adhesions. Nat Immunol. 2010; 11(10):953-61. PMC: 2943564. DOI: 10.1038/ni.1936. View

17.

Teo G, Ankrum J, Martinelli R, Boetto S, Simms K, Sciuto T . Mesenchymal stem cells transmigrate between and directly through tumor necrosis factor-α-activated endothelial cells via both leukocyte-like and novel mechanisms. Stem Cells. 2012; 30(11):2472-86. PMC: 3479371. DOI: 10.1002/stem.1198. View

18.

Chauveau A, Pirgova G, Cheng H, De Martin A, Zhou F, Wideman S . Visualization of T Cell Migration in the Spleen Reveals a Network of Perivascular Pathways that Guide Entry into T Zones. Immunity. 2020; 52(5):794-807.e7. PMC: 7237890. DOI: 10.1016/j.immuni.2020.03.010. View

19.

Wendt T, Taylor D, Trybus K, Taylor K . Three-dimensional image reconstruction of dephosphorylated smooth muscle heavy meromyosin reveals asymmetry in the interaction between myosin heads and placement of subfragment 2. Proc Natl Acad Sci U S A. 2001; 98(8):4361-6. PMC: 31840. DOI: 10.1073/pnas.071051098. View

20.

Schwab S, Pereira J, Matloubian M, Xu Y, Huang Y, Cyster J . Lymphocyte sequestration through S1P lyase inhibition and disruption of S1P gradients. Science. 2005; 309(5741):1735-9. DOI: 10.1126/science.1113640. View