Csenge K. Rezi

All Publications

• KIF13B controls ciliary protein content by promoting endocytic retrieval and suppressing release of large extracellular vesicles from cilia. Current biology : CB Rezi, C. K., Frei, A., Campestre, F., Boldt, K., Mary, B., Fixdahl, A. M., With Petersen, A., Sicot, A., Berggreen, C. R., Laplace, J., Johansen, S. L., Sorensen, J. K., Chamlali, M., Berchtold, M. W., Christensen, S. T., Anvarian, Z., May-Simera, H. L., Pedersen, L. B. 2025

  Abstract

  Dynamic control of ciliary membrane protein content is crucial for the organelle's homeostasis and signaling function and involves removal of ciliary components by intraflagellar transport (IFT) and BBSome-mediated export, endocytic retrieval, and/or extracellular vesicle (EV) shedding. We report that the kinesin-3 motor KIF13B regulates ciliary protein composition and EV shedding in cultured kidney epithelial cells, with effects that vary over time. In early stages of ciliation, Kif13b-/- cells aberrantly accumulate polycystin-2 (PC2) within cilia and release large EVs enriched with CCDC198 and the centriole distal appendage protein CCDC92, which also localizes to the ciliary tip. These cells also produce fewer small EVs through the neutral sphingomyelinase 2 pathway. Upon cilia maturation, Kif13b-/- cells accelerate large EV release of numerous ciliary proteins, including PC2, BBSome, and IFT components, which correlates with gradual depletion of CCDC92 and PC2 from the ciliary tip and shaft, respectively. Furthermore, over time, Kif13b-/- cells show an upregulation in the release of small EVs, which differ in composition from wild-type small EVs. Specifically, mutant small EVs lack several proteins that are enriched in small EVs from BBSome-deficient cells, including palmitoyl transferase ZDHHC5, which localizes to cilia where it accumulates upon BBSome dysfunction and regulates ciliary length and PC2 levels. Our results suggest that KIF13B acts at the level of centriole distal appendages to limit ciliary protein entry and promote endocytic retrieval downstream of the BBSome, thereby suppressing EV release from cilia. Furthermore, the ciliary localization of CCDC198 and ZDHHC5 indicates they are potential novel ciliopathy candidates.

  View details for DOI 10.1016/j.cub.2025.08.022

  View details for PubMedID 40930094

• DLG1 functions upstream of SDCCAG3 and IFT20 to control ciliary targeting of polycystin-2. EMBO reports Rezi, C. K., Aslanyan, M. G., Diwan, G. D., Cheng, T., Chamlali, M., Junger, K., Anvarian, Z., Lorentzen, E., Pauly, K. B., Afshar-Bahadori, Y., Fernandes, E. F., Qian, F., Tosi, S., Christensen, S. T., Pedersen, S. F., Strømgaard, K., Russell, R. B., Miner, J. H., Mahjoub, M. R., Boldt, K., Roepman, R., Pedersen, L. B. 2024; 25 (7): 3040-3063

  Abstract

  Polarized vesicular trafficking directs specific receptors and ion channels to cilia, but the underlying mechanisms are poorly understood. Here we describe a role for DLG1, a core component of the Scribble polarity complex, in regulating ciliary protein trafficking in kidney epithelial cells. Conditional knockout of Dlg1 in mouse kidney causes ciliary elongation and cystogenesis, and cell-based proximity labeling proteomics and fluorescence microscopy show alterations in the ciliary proteome upon loss of DLG1. Specifically, the retromer-associated protein SDCCAG3, IFT20, and polycystin-2 (PC2) are reduced in the cilia of DLG1-deficient cells compared to control cells. This phenotype is recapitulated in vivo and rescuable by re-expression of wild-type DLG1, but not a Congenital Anomalies of the Kidney and Urinary Tract (CAKUT)-associated DLG1 variant, p.T489R. Finally, biochemical approaches and Alpha Fold modelling suggest that SDCCAG3 and IFT20 form a complex that associates, at least indirectly, with DLG1. Our work identifies a key role for DLG1 in regulating ciliary protein composition and suggests that ciliary dysfunction of the p.T489R DLG1 variant may contribute to CAKUT.

  View details for DOI 10.1038/s44319-024-00170-1

  View details for PubMedID 38849673

  View details for PubMedCentralID PMC11239879