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Hoogvliet, I. A.

Publications and source records attributed to Hoogvliet, I. A..

2 recordsLinked to original sources

Recruitment of Fpt1 to tRNA genes requires TFIIIB and the N-terminal TPR array of TFIIIC subunit {tau}131

Transfer-RNA genes (tDNAs) in budding yeast recruit varying amounts of Fpt1, a regulator of RNA polymerase III (RNAPIII) occupancy. Fpt1 occupancy resembles that of the general transcription factor TFIIIC but how Fpt1 is recruited to tDNAs remains unclear. Here we show that both TFIIIB and TFIIIC are required for Fpt1 binding under active as well as repressive RNAPIII conditions. Depletion of TFIIIB reduced Fpt1 occupancy without affecting TFIIIC. In contrast, TFIIIC depletion led to reduced Fpt1 and a gene-specific reduction in TFIIIB occupancy. Moreover, upon depletion of TFIIIC, Fpt1 and TFIIIB were lost to different extents. We identified the C-terminal intrinsically disordered region of Fpt1 as critical for increased Fpt1 binding under repressive conditions. Within this region, a short -helix was predicted to interact with the N-terminal tetratricopeptide repeat array of the TFIIIC subunit {tau}131, a region also known to interact with TFIIIB. Deletion of this -helix abrogated stress-induced Fpt1 recruitment to tDNAs, as did mutations in the predicted interaction surface of {tau}131, while having a milder effect on TFIIIB occupancy. Together, these findings uncovered a dual and dynamic mechanism of Fpt1 recruitment to tDNAs with independent contributions of TFIIIB and TFIIIC.

molecular biology↗

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↗