CD43 interaction with ezrin-radixin-moesin (ERM) proteins regulates T-cell trafficking and CD43 phosphorylation

Cannon, Judy L.; Mody, Purvi D.; Blaine, Kelly M.; Chen, E. J.; Nelson, Andrew D. L.; Sayles, L. J.; Moore, Tamson V.; Clay, Bryan S.; Dulin, Nickolai O.; Shilling, Rebecca A.; Burkhardt, Janis K.; Sperling, Anne I.

doi:10.1091/mbc.e10-07-0586

Cited by 27 publications

(34 citation statements)

References 40 publications

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“…CD43 regulates critical cellular functions, including T cell trafficking (Cannon et al 2011). The activation of the T cell receptor (TCR) enhances the binding of ezrin to CD43, which induces the formation of a scaffold between the membrane and the cytoskeleton at the contact zone between the T cells and the antigen-presenting cells (APC) (Roumier et al (2001).…”

Section: Ezrin Counterparts: From Receptors To Scaffold Proteinsmentioning

confidence: 99%

“…Ezrin also plays an important role in the distal pole complex (DPC) at the opposite site of the immunological synapse (Allenspach et al 2001; Shaffer et al 2009). Ezrin binding is crucial for the phosphorylation of CD43 during T lymphocyte activation (Cannon et al 2011). Similarly, the activation of Rac1 induces ezrin dephosphorylation and regulates its binding to membrane receptors at the DPC of T lymphocytes (Fig.…”

Section: Clinical Implications Of Ezrin In Asthmamentioning

confidence: 99%

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Ezrin Orchestrates Signal Transduction in Airway Cells

Yin

Duan

Ulloa

et al. 2017

Reviews of Physiology, Biochemistry and Pharmacology

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Ezrin is a critical structural protein that organizes receptor complexes and orchestrates their signal transduction. In this study, we review the ezrin-meditated regulation of critical receptor complexes, including the epidermal growth factor receptor (EGFR), CD44, vascular cell adhesion molecule (VCAM), and the deleted in colorectal cancer (DCC) receptor. We also analyze the ezrin-meditated regulation of critical pathways associated with asthma, such as the RhoA, Rho-associated protein kinase (ROCK), and protein kinase A (cAMP/PKA) pathways. Mounting evidence suggests that ezrin plays a role in controlling airway cell function and potentially contributes to respiratory diseases. Ezrin can participate in asthma pathogenesis by affecting bronchial epithelium repair, T lymphocyte regulation, and the contraction of the airway smooth muscle cells. These studies provide new insights for the design of novel therapeutic strategies for asthma treatment.

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Section: Ezrin Counterparts: From Receptors To Scaffold Proteinsmentioning

confidence: 99%

Section: Clinical Implications Of Ezrin In Asthmamentioning

confidence: 99%

Ezrin Orchestrates Signal Transduction in Airway Cells

Yin

Duan

Ulloa

et al. 2017

Reviews of Physiology, Biochemistry and Pharmacology

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“…In addition to innate immune mechanisms, previous studies suggest that CD43 is involved primarily in three main functions: (1) cellular adhesion due to structural characteristics of the extracellular domain, which has O-glycosylated mucinlike aminoacids and sialic acid residues (39,40); (2) T cell activation and migration via cleavage of the CD43 extracellular domain, which interacts with endogenous lectin coreceptors (41) and proteins of the cytoskeleton (42) (CD43 uses E-selectin as a ligand on endothelial cells to regulate migration to sites of inflammation [41,43]); and (3) CD43 regulates T cell trafficking to lymph nodes via phosphorylation of a specific serine residue in the CD43 intracellular domain (42,44,45). Moreover, CD43 forms clusters via thiol group oxidation on lymphocytes.…”

Section: Original Researchmentioning

confidence: 99%

Common Polymorphisms in the CD43 Gene Region Are Associated with Tuberculosis Disease and Mortality

Campo

Randhawa

Dunstan

et al. 2015

Am J Respir Cell Mol Biol

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CD43, a surface glycoprotein, regulates Mycobacterium tuberculosis macrophage binding, replication, and proinflammatory cytokine induction in a murine model. We hypothesized that single-nucleotide polymorphisms (SNPs) in the CD43 gene region are associated with human tuberculosis (TB) susceptibility. We performed a casepopulation study in discovery (352 TB cases and 382 control subjects) and validation cohorts (339 TB cases and 376 control subjects). We examined whether 11 haplotype-tagging SNPs in the CD43 gene region were associated with tuberculous meningitis (TBM) and pulmonary TB (PTB) in Vietnam. Three SNPs from the CD43 gene region were associated with TB susceptibility with a genotypic model. The association fit a recessive genetic model and was greater for TBM than for PTB (for TBM: rs4788172, odds ratio [OR], 1.64; 95% confidence interval [CI], 1.04-2.59, rs17842268 [OR, 2.20; 95% CI, 1.29-3.76, and rs12596308 [OR, 2.38; 95% CI, 1.47-3.89]). Among TBM cases, rs17842268 was associated with decreased survival (hazard ratio, 2.7; 95% CI, 1.1-6.5; P = 0.011). In addition, rs12596308 and rs17842268 were associated with focal neurologic deficit at TBM presentation. Our data suggest that CD43 polymorphisms are associated with TB susceptibility, disease manifestations, and worse outcomes. To our knowledge, this is the first report that links CD43 genetic variants with susceptibility and outcome from a disease.

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“…Leukosialin, or CD43, is a sialoglycoprotein found on the cell membrane of all leukocytes and has been implicated in the regulation of CD4+ T cell trafficking and T cell migration and activation (80–82). CD43 is expressed in microglia, with higher expression in reactive cells as compared to resting cells (83).…”

Section: Resultsmentioning

confidence: 99%

Buprenorphine Decreases the CCL2-Mediated Chemotactic Response of Monocytes

Carvallo

Lopez

Fei

et al. 2015

The Journal of Immunology

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Despite successful cART, approximately 60% of HIV infected people exhibit HIV associated neurocognitive disorders (HAND). CCL2 is elevated in the CNS of infected people with HAND and mediates monocyte influx into the CNS, which is critical in neuroAIDS. Many HIV infected opiate abusers have increased neuroinflammation that may augment HAND. Buprenorphine is used to treat opiate addiction. However, there are few studies that examine its impact on HIV neuropathogenesis. We show that buprenorphine reduces the chemotactic phenotype of monocytes. Buprenorphine decreases the formation of membrane projections in response to CCL2. It also decreases CCL2-induced chemotaxis and mediates a delay in reinsertion of the CCL2 receptor, CCR2, into the cell membrane after CCL2-mediated receptor internalization, suggesting a mechanism of action of buprenorphine. Signaling pathways in CCL2-induced migration include increased phosphorylation of p38 MAPK and of the junctional protein JAM-A. We show that buprenorphine decreases these phosphorylations in CCL2-treated monocytes. Using DAMGO, CTAP, and Nor-BNI, we demonstrate that the effect of buprenorphine on CCL2 signaling is opioid receptor mediated. To identify additional potential mechanisms by which buprenorphine inhibits CCL2-induced monocyte migration, we performed proteomic analyses to characterize additional proteins in monocytes whose phosphorylation after CCL2 treatment was inhibited by buprenorphine. Leukosialin and S100A9, were identified and had not been shown previously be involved in monocyte migration. We propose that buprenorphine limits CCL2-mediated monocyte transmigration into the CNS, thereby reducing neuroinflammation characteristic of HAND. Our findings underscore the use of buprenorphine as a therapeutic for neuroinflammation as well as for addiction.

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CD43 interaction with ezrin-radixin-moesin (ERM) proteins regulates T-cell trafficking and CD43 phosphorylation

Abstract: CD43 interaction with ERM proteins regulates CD43 phosphorylation and T-cell migration. CD43 phosphorylation can also drive CD43 localization in T-cells independently of ERM association.

Cited by 27 publications

References 40 publications

Ezrin Orchestrates Signal Transduction in Airway Cells

Ezrin Orchestrates Signal Transduction in Airway Cells

Common Polymorphisms in the CD43 Gene Region Are Associated with Tuberculosis Disease and Mortality

Buprenorphine Decreases the CCL2-Mediated Chemotactic Response of Monocytes

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