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.

Grina/TMBIM3 modulates voltage-gated Ca2.2 Ca channels in a G-protein-like manner.

Grina/TMBIM3 is a poorly characterized transmembrane protein with a broad expression pattern in mammals and with a very ancient origin within eukaryotes. Although initially characterized as an NMDA-receptor associated subunit, there is increasing evidence that Grina/TMBIM3 is involved in the unfolded protein response and controls apoptosis via regulation of Ca homeostasis. Here, we investigate a putative direct interaction of Grina/TMBIM3 with voltage gated Ca channels, in particular with the Ca2.

The two-pore channel TPC1 is required for efficient protein processing through early and recycling endosomes.

Two-pore channels (TPCs) are localized in endo-lysosomal compartments and assumed to play an important role for vesicular fusion and endosomal trafficking. Recently, it has been shown that both TPC1 and 2 were required for host cell entry and pathogenicity of Ebola viruses. Here, we investigate the cellular function of TPC1 using protein toxins as model substrates for distinct endosomal processing routes.

Ablation of Ca(V)2.1 voltage-gated Ca²⁺ channels in mouse forebrain generates multiple cognitive impairments.

Voltage-gated Ca(V)2.1 (P/Q-type) Ca²⁺ channels located at the presynaptic membrane are known to control a multitude of Ca²⁺-dependent cellular processes such as neurotransmitter release and synaptic plasticity. Our knowledge about their contributions to complex cognitive functions, however, is restricted by the limited adequacy of existing transgenic Ca(V)2.

Identification of cysteine residues in human cationic amino acid transporter hCAT-2A that are targets for inhibition by N-ethylmaleimide.

In most cells, cationic amino acids such as l-arginine, l-lysine, and l-ornithine are transported by cationic (CAT) and y(+)L (y(+)LAT) amino acid transporters. In human erythrocytes, the cysteine-modifying agent N-ethylmaleimide (NEM) has been shown to inhibit system y(+) (most likely CAT-1), but not system y(+)L (Devés, R., Angelo, S.

Tetraspanin-13 modulates voltage-gated CaV2.2 Ca2+ channels.

Integration of voltage-gated Ca(2+) channels in a network of protein-interactions is a crucial requirement for proper regulation of channel activity. In this study, we took advantage of the specific properties of the yeast split-ubiquitin system to search for and characterize so far unknown interaction partners of CaV2 Ca(2+) channels. We identified tetraspanin-13 (TSPAN-13) as an interaction partner of the α1 subunit of N-type CaV2.