A multiscale model of the regulation of aquaporin 2 recycling

Research output: Contribution to journalResearch articleContributedpeer-review



The response of cells to their environment is driven by a variety of proteins and messenger molecules. In eukaryotes, their distribution and location in the cell are regulated by the vesicular transport system. The transport of aquaporin 2 between membrane and storage region is a crucial part of the water reabsorption in renal principal cells, and its malfunction can lead to Diabetes insipidus. To understand the regulation of this system, we aggregated pathways and mechanisms from literature and derived three models in a hypothesis-driven approach. Furthermore, we combined the models to a single system to gain insight into key regulatory mechanisms of Aquaporin 2 recycling. To achieve this, we developed a multiscale computational framework for the modeling and simulation of cellular systems. The analysis of the system rationalizes that the compartmentalization of cAMP in renal principal cells is a result of the protein kinase A signalosome and can only occur if specific cellular components are observed in conjunction. Endocytotic and exocytotic processes are inherently connected and can be regulated by the same protein kinase A signal.


Original languageEnglish
Article number16
Journalnpj systems biology and applications
Issue number16
Publication statusPublished - 9 May 2022

External IDs

PubMedCentral PMC9085758
Scopus 85129526359
Mendeley d46bae56-e0a0-3f64-a296-6c4b7eaedd9f
ORCID /0000-0003-2848-6949/work/141543350


Sustainable Development Goals


  • Aquaporin 2/genetics, Biological Transport, Cyclic AMP-Dependent Protein Kinases/metabolism, Water/metabolism