Two-pore channel protein TPC1 is a determining factor for the adaptation of proximal tubular phosphate handling.

Aim: Two-pore channels (TPCs) constitute a small family of cation channels expressed in endo-lysosomal compartments. TPCs have been characterized as critical elements controlling Ca -mediated vesicular membrane fusion and thereby regulating endo-lysosomal vesicle trafficking. Exo- and endocytotic trafficking and lysosomal degradation are major mechanisms of adaption of epithelial transport.

Two-Pore Channels Regulate Expression of Various Receptors and Their Pathway-Related Proteins in Multiple Ways.

Two-pore channels (TPCs) constitute a small family of ion channels within membranes of intracellular acidic compartments, such as endosomes and lysosomes. They were shown to provide transient and locally restricted Ca-currents, likely responsible for fusion and/or fission events of endolysosomal membranes and thereby for intracellular vesicle trafficking. Genetic deletion of TPCs not only affects endocytosis, recycling, and degradation of various surface receptors but also uptake and impact of bacterial protein toxins and entry and intracellular processing of some types of viruses.

Two-pore channels affect EGF receptor signaling by receptor trafficking and expression.

Two-pore channels (TPCs) are key components for regulating Ca current from endosomes and lysosomes to the cytosol. This locally restricted Ca current forms the basis for fusion and fission events between endolysosomal membranes and thereby for intracellular trafficking processes. Here, we study the function of TPC1 and TPC2 for uptake, recycling, and degradation of epidermal growth factor receptor (EGFR) using a set of TPC knockout cells.

Modulation of voltage-gated Ca2.2 Ca channels by newly identified interaction partners.

Voltage-gated Ca channels are typically integrated in a complex network of protein-protein-interactions, also referred to as Ca channel nanodomains. Amongst the neuronal Ca2 channel family, Ca2.2 is of particular importance due to its general role for signal transmission from the periphery to the central nervous system, but also due to its significance for pain perception.

Genetic Inactivation of Two-Pore Channel 1 Impairs Spatial Learning and Memory.

Two-pore channels (TPCs) constitute a small family of cation channels that are localized in membranes of endosomal and lysosomal compartments. Although their roles for vesicular fusion and endolysosomal trafficking have been investigated, our knowledge on their expression pattern and higher order functions in the murine brain is still limited. Western blot analysis indicated a broad expression of TPC1 in the neocortex, cerebellum and hippocampus.