Physiology and Pathology of Ion Transport
Head of the Group
Prof. Dr. Thomas Jentsch
Ion transport across cellular membranes is important for cellular homeostasis and has integrative functions such as transepithelial transport or neuronal signal transduction. We study these processes at various levels, from biophysical analysis of transport proteins, structure-function analysis, role in cellular functions such as cell volume regulation or endocytosis, to the role in the organism. The physiological role of ion transport proteins has often been gleaned from pathologies resulting from their inactivation in human diseases or in mouse models. We have discovered several human ‘channelopathies’ and have generated and analyzed many mouse models. We focus on CLC chloride channels and transporters, KCC potassium-chloride co-transporters, and KCNQ potassium channels, and are extending our studies to other channel classes. Their mutational Inactivation led to pathologies ranging from epilepsy, deafness, lysosomal storage disease to osteopetrosis, kidney stones and hypertension. We are particularly interested in the control of neuronal excitability and in the role of chloride and pH in endosomes and lysosomes.
Recently we have identified the long-sought volume-regulated anion channel VRAC by a genome-wide siRNA screen. This important channel has been known from biophysical studies for decades, but the underlying proteins have remained unknown in spite of many efforts. We showed that this channel is not only crucial for regulatory volume decrease of cells, but also for the uptake and efflux of organic substrates like taurine and glutamate, with profound implications for extracellular signaling and pathologies like stroke. This has swung open the door to an important new research area which we will vigorously explore in the next years.