A fluorescent sensor for real-time monitoring of DPP8/9 reveals crucial roles in immunity and cancer
Weiss K, Agarkova Y, Zwosta A, Hoevel S, Himmelreich AK, Shumanska M, Etich J, Poschmann G, Brachvogel B, Bogeski I, Mielenz D, Riemer J (2025)
Publication Language: English
Publication Type: Journal article
Publication year: 2025
Journal
Book Volume: 8
Article Number: e202403076
Journal Issue: 8
Abstract
Dipeptidyl peptidases 8 and 9 (DPP8/9) are critical for the quality control of mitochondrial and endoplasmic reticulum protein import, immune regulation, cell adhesion, and cell migration. Dysregulation of DPP8/9 is associated with pathologies including tumorigenesis and inflammation. Commonly, DPP8/9 activity is analysed by in vitro assays using artificial substrates, which allow neither continuously monitoring DPP8/9 activity in individual, living cells nor detecting effects from endogenous interactors and posttranslational modifications. Here, we developed DiPAK (for DPP8/9 activity sensor based on AK2), a ratiometric genetically encoded fluorescent sensor, which enables studying DPP8/ 9 activity in living cells. Using DiPAK, we determined the dynamic range of DPP8/9 activity in cells overexpressing or lacking DPP9. We identified distinct activity levels among melanoma cell lines and found that LPS-induced primary B-cell activation depends on DPP8/9 as the absence of DPP8/9 activity results in apoptotic but not pyroptotic cell death. Consistently, we observed increasing DPP8/9 activity during B-cell maturation. Overall, DiPAK is a versatile tool for real-time single-cell monitoring of DPP8/9 activity in a broad range of cells and organisms.
Authors with CRIS profile
Ann-Kathrin Himmelreich
Department of Molecular Immunology
Dirk Mielenz
Department of Molecular Immunology
Involved external institutions
Universität zu Köln
Germany (DE)
Universitätsklinikum Göttingen
Germany (DE)
Universitätsklinikum Köln
Germany (DE)
Universitätsklinikum Düsseldorf
Germany (DE)
Germany (DE)
Universitätsklinikum Göttingen
Germany (DE)
Universitätsklinikum Köln
Germany (DE)
Universitätsklinikum Düsseldorf
Germany (DE)
How to cite
APA:
Weiss, K., Agarkova, Y., Zwosta, A., Hoevel, S., Himmelreich, A.-K., Shumanska, M.,... Riemer, J. (2025). A fluorescent sensor for real-time monitoring of DPP8/9 reveals crucial roles in immunity and cancer. Life Science Alliance, 8(8). https://doi.org/10.26508/lsa.202403076
MLA:
Weiss, Konstantin, et al. "A fluorescent sensor for real-time monitoring of DPP8/9 reveals crucial roles in immunity and cancer." Life Science Alliance 8.8 (2025).
BibTeX: Download