Pharmacology for Natural Sciences

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Endolysomal cation channels

The endolysosomal system consists of a variety of organelles including different types of endosomes, phagosomes and lysosomes. These organells play crucial roles in diverse cellular processes such as receptor trafficking, degradation of proteins, endocytosis, secretion and Ca2+ signaling. Our group is interested in ion channels that control the function of endolysomal organelles. A particular focus is on Two-Pore Channels (TPCs) that are structurally related to the members of the TRP channel family, in particular the TRPML channels. Our laboratory was among the first groups to clone and funcionally charcaterize TPCs (Zong et al. 2009). We use a variety of methods, in particular endolysosomal patch-clamp technology, imaging, molecular biology and physiological assays to exmine the in vivo function of these channels. Using genetic mouse models, we found that TPCs are involved in cellular trafficking of viruses and receptors of the plasma membrane, as well as skin pigmention and neoangiogenesis in the retina. Based on these basic studies, we are currently exploring the therapeutic potential of TPCs and TRPMLs.

 ion-channel         tpc2

Phylogenetic tree of the TRP ion channel                    Potential role of TPC2 in the pathomechanism of neovascular             family including TPC1 and TPC2                                  age-dependent macular degeneration

Further reading

Li et al. (2021) Life Sci Alliance

Chen et al. (2020) Sci Adv

Chen et al. (2017) Nat Protoc

Sakurai et al. (2015) Science

Grimm et al. (2014) Nat Commun

Zong et al. (2009) Pflugers Arch