P05 - Proteomic analysis and physiological function of the two pore channel TPC1
Two-pore channels have been identified as essential components of NAADP-induced Ca2+-signalling in endolysosomal compartments. Their native subunit architecture, biophysical properties and gating determinants are unknown. Therefore, we aim to (1) identify the molecular composition of native TPC1 complexes, (2) unravel their tissue distribution and subcellular localization, (3) study the proteomic and functional changes in compartments along the secretory and endocytic pathways induced by genetic ablation of TPC1 and (4) characterize their cellular function and physiological role in kidney and other epithelia.
The figure shows the expression pattern of TPC1 (red) in kidney. Lotus-Lectin (green) is a marker for the proximal tubule and highlights predominant expression of TPC1 in this part of the nephron. The inset shows the corresponding immunohistochemical staining with a TPC1 knock-out mouse.