ORCID Profile
0000-0002-5071-9000
Current Organisation
Radboudumc
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Publisher: Elsevier BV
Date: 06-2022
DOI: 10.1016/J.CELREP.2022.111006
Abstract: T cells depend on the phosphatase CD45 to initiate T cell receptor signaling. Although the critical role of CD45 in T cells is established, the mechanisms controlling function and localization in the membrane are not well understood. Moreover, the regulation of specific CD45 isoforms in T cell signaling remains unresolved. By using unbiased mass spectrometry, we identify the tetraspanin CD53 as a partner of CD45 and show that CD53 controls CD45 function and T cell activation. CD53-negative T cells (Cd53
Publisher: Springer Science and Business Media LLC
Date: 08-05-2015
Publisher: American Association for the Advancement of Science (AAAS)
Date: 13-11-2012
DOI: 10.1126/SCISIGNAL.2003113
Abstract: Antibody-producing B cells require CD37-dependent integrin signaling for long-term survival.
Publisher: Public Library of Science (PLoS)
Date: 07-09-2017
Publisher: Springer Science and Business Media LLC
Date: 13-08-2012
DOI: 10.1038/CMI.2012.21
Publisher: Oxford University Press (OUP)
Date: 29-10-2013
DOI: 10.1189/JLB.0813440
Abstract: The plasma membrane of immune cells is a highly organized cell structure that is key to the initiation and regulation of innate and adaptive immune responses. It is well-established that immunoreceptors embedded in the plasma membrane have a nonrandom spatial distribution that is important for coupling to components of intracellular signaling cascades. In the last two decades, specialized membrane microdomains, including lipid rafts and TEMs, have been identified. These domains are preformed structures (“physical entities”) that compartmentalize proteins, lipids, and signaling molecules into multimolecular assemblies. In APCs, different microdomains containing immunoreceptors (MHC proteins, PRRs, integrins, among others) have been reported that are imperative for efficient pathogen recognition, the formation of the immunological synapse, and subsequent T cell activation. In addition, recent work has demonstrated that tetraspanin microdomains and lipid rafts are involved in BCR signaling and B cell activation. Research into the molecular mechanisms underlying membrane domain formation is fundamental to a comprehensive understanding of membrane-proximal signaling and APC function. This review will also discuss the advances in the microscopy field for the visualization of the plasma membrane, as well as the recent progress in targeting microdomains as novel, therapeutic approach for infectious and malignant diseases.
Publisher: Cold Spring Harbor Laboratory
Date: 22-12-2020
DOI: 10.1101/2020.12.21.423770
Abstract: Macrophage recruitment during sterile inflammation and infection is essential to clear pathogens, apoptotic cells and debris. However, persistent macrophage accumulation leads to chronic inflammation. Platelets are emerging as key modulators of the inflammatory response. Here, we identify that platelet C-type-lectin-like receptor-2 (CLEC-2) is a crucial immunomodulatory receptor through the interaction with podoplanin, upregulated on inflammatory macrophages. Mechanistically, platelet CLEC-2 upregulates the expression of podoplanin and its co-ligands CD44 and ERM proteins, leading to actin rearrangement and promotion of cell migration this is mimicked by recombinant CLEC-2-Fc (rCLEC-2-Fc). Treatment of LPS-challenged mice with rCLEC-2-Fc induces a rapid emigration of peritoneal macrophages to mesenteric lymph nodes, through a gradient generated by the podoplanin ligand, CCL21, to prime T cells. We propose that crosslinking podoplanin using rCLEC-2-Fc is a novel, cell-specific strategy to accelerate macrophage removal from the site of inflammation, and hence promote the resolution of the inflammatory response. Persistent macrophage accumulation in inflamed tissue leads to chronic inflammation and organ damage. Bourne et al. identify recombinant CLEC-2-Fc crosslinking podoplanin on inflammatory macrophages, as a cell-specific strategy to accelerate their emigration to draining lymph nodes, and reduce local inflammation.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 09-05-2017
DOI: 10.1126/SCISIGNAL.AAG2755
Abstract: The tetraspanin protein CD53 recruits the kinase PKCβ to the plasma membrane to activate signaling in B cells.
Publisher: Springer Science and Business Media LLC
Date: 17-07-2015
DOI: 10.1038/SREP12201
Abstract: The spatial organization of membrane proteins in the plasma membrane is critical for signal transduction, cell communication and membrane trafficking. Tetraspanins organize functional higher-order protein complexes called ‘tetraspanin-enriched microdomains (TEMs)’ via interactions with partner molecules and other tetraspanins. Still, the nanoscale organization of TEMs in native plasma membranes has not been resolved. Here, we elucidated the size, density and distribution of TEMs in the plasma membrane of human B cells and dendritic cells using dual color stimulated emission depletion (STED) microscopy. We demonstrate that tetraspanins form in idual nanoclusters smaller than 120 nm and quantified that a single tetraspanin CD53 cluster contains less than ten CD53 molecules. CD53 and CD37 domains were adjacent to and displayed only minor overlap with clusters containing tetraspanins CD81 or CD82. Moreover, CD53 and CD81 were found in closer proximity to their partners MHC class II and CD19 than to other tetraspanins. Although these results indicate that tetraspanin domains are adjacently positioned in the plasma membrane, they challenge the current view of the tetraspanin web of multiple tetraspanin species organized into a single domain. This study increases the molecular understanding of TEMs at the nanoscale level which is essential for comprehending tetraspanin function in cell biology.
Publisher: American Society of Hematology
Date: 07-02-2019
DOI: 10.1182/BLOOD-2018-08-867267
Abstract: Thrombosis is a frequent, life-threatening complication of systemic infection associated with multiple organ damage. We have previously described a novel mechanism of inflammation-driven thrombosis induced by Salmonella Typhimurium infection of mice. Thrombosis in the liver develops 7 days after infection, persisting after the infection resolves, and is monocytic cell dependent. Unexpectedly, thrombosis was not prominent in the spleen at this time, despite carrying a similar bacterial burden as the liver. In this study, we show that thrombosis does occur in the spleen but with strikingly accelerated kinetics compared with the liver, being evident by 24 hours and resolving rapidly thereafter. The distinct kinetics of thrombosis and bacterial burden provides a test of the hypothesis that thrombi form in healthy vessels to trap or remove bacteria from the circulation, often termed immunothrombosis. Remarkably, despite bacteria being detected throughout infected spleens and livers in the early days of infection, immunohistological analysis of tissue sections show that thrombi contain very low numbers of bacteria. In contrast, bacteria are present throughout platelet aggregates induced by Salmonella in vitro. Therefore, we show that thrombosis develops with organ-specific kinetics and challenge the universality of immunothrombosis as a mechanism to capture bacteria in vivo.
No related grants have been discovered for Malou Zuidscherwoude.