Biology subjects

van Deventer, S. J.

Publications and source records attributed to van Deventer, S. J..

3 recordsLinked to original sources

bioRxiv2025

Tetraspanin CD82 reduces the formation of CADM1 oligomers

CD82 is a member of the tetraspanin protein superfamily and known as a metastasis suppressor. We identified cell adhesion molecule 1 (CADM1) as an interaction partner of CD82. CADM1 mediates cell adhesion by forming cis and trans oligomers that connect membranes. We show that CD82 reduces the formation of CADM1 oligomers when solubilized by detergent, on liposomes and in cellulo using Jurkat T-cells. Our data is consistent with a 1:1 complex of CD82 and CADM1 in cis that leaves the CADM1 trans-interaction site accessible. Cryo-electron microscopy of the CD82:CADM1 heterodimer suggests an interaction site between the large-extracellular loop of CD82 and an Ig-like domain of CADM1. Consistently, liposomes coupled with CADM1 ectodomain show reduced clustering when reconstituted with CD82. We hypothesize that CD82 may affect spacing of the transmembrane helices of CADM1, possibly by interacting with the extracellular Ig-like domains and hence disrupting CADM1 oligomerization between membranes.

biochemistry↗

bioRxiv2023

Glycosylation differentially affects immune cell-specific tetraspanins CD37 and CD53

Tetraspanin proteins play an important role in many cellular processes as they are key organizers of different receptors on the plasma membrane. Most tetraspanins are highly glycosylated at their large extracellular loop, but the function of this post-translational modification remains largely unstudied. In this study we investigated the effects of glycosylation of CD37 and CD53, two tetraspanins important for cellular and humoral immunity. Broad and cell-specific repertoires of N-glycosylated CD37 and CD53 were observed in human B cells. We generated different glycosylation mutants of CD37 and CD53 and analyzed their localization, nanoscale organization and partner protein interaction capacity. Abrogation of glycosylation in CD37 revealed the importance of this modification for CD37 surface expression, whereas neither surface expression nor nanoscale organization of CD53 was affected by its glycosylation. CD37 interaction with its known partner proteins, CD20 and IL-6R, was not affected by glycosylation, other than via its changed subcellular localization. Surprisingly, glycosylation was found to inhibit the interaction between CD53 and its partner proteins CD45 and CD20. Together, our data show that tetraspanin glycosylation affects their function in immune cells, which adds another layer of regulation to tetraspanin-mediated membrane organization.

cell biology↗

bioRxiv2019

Dynamic regulation of CD45 by tetraspanin CD53

T cells are central to the adaptive immune response, playing a role in both the direct and indirect killing of pathogens and transformed cells. The activation of T cells is the result of a complex signaling cascade, initiated at the T cell receptor (TCR), and ending with the induction of proliferation. CD45, a member of the protein tyrosine phosphatase family, is one of the most abundant membrane proteins on T cells and functions by regulating activation directly downstream of the TCR. As a result of alternative splicing, CD45 can be expressed in multiple isoforms, naive T cells express the CD45RA isoform, while activated T cells gain expression of CD45RO, which has been proposed to increase signaling. Though the importance of CD45 in TCR signaling, proliferation and cytokine production is well established, little is known about the regulation of CD45 activity. We discovered that the immune-specific tetraspanin CD53 directly affects the stability and function of CD45RO in T cells. We have identified CD53 as a T cell co-stimulatory molecule in primary human and murine cells. Furthermore, we have shown that the absence of CD53 leads to an altered CD45 isoform expression as a result of decreased CD45RO stability on the cell surface. This instability was accompanied by increased mobility as measured by FRAP. Together, this indicates that CD53 functions as a stabilizer of CD45RO, and therefore as a positive regulator of TCR signaling at the T cell surface. Our data provides novel insight into the role of tetraspanins in the regulation of immune signaling and may provide a new avenue for the regulation of T cell signaling.

immunology↗