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Klugbauer group


I. Voltage gated calcium channels

We are investigating the molecular assembly and function of voltage gated calcium channels. Cav channels are embedded in a network of auxiliary and modulatory proteins, which affect the channel´s membrane targeting, regulation and biophysical properties. Yeast two hybrid systems allowed us to identify and characterize a number of novel interaction partners of Cav2.2 calcium channels. By using knockout models, we uncovered important aspects of the contribution of Cav´s for learning and memory.

Key Papers:
1. Lacinova L, Mallmann RT, Jurkovičová-Tarabová B, Klugbauer N (2020) Modulation of voltage-gated Cav2.2 Ca2+ channels by newly identified interaction partners. Channels (Austin), 14, 380-392.
2. Mallmann, R. T., Moravcikova, L., Ondacova, K., Lacinova, L., Klugbauer, N. (2019). GRINA/TMBIM3 modulates voltage-gated Cav2.2 Ca2+ channels in a G-protein-like manner. Cell Calcium, 80, 71-78.
3. Mallmann, R. T., Ondacova, K., Moravcikova, L., Jurkovičová-Tarabová, B., Pavlovicova, M., Lichvarova, L., Kominkova, V., Klugbauer, N., Lacinova, L. (2019). Four novel interaction partners demonstrate diverse modulatory effects on voltage-gated Cav2.2 Ca2+ channels. Pflugers Arch, 471, 861-874.
4. Normann, C., Frase, S., Haug, V., von Wolff, G., Clark, K., Münzer, P., Dorner, A., Scholliers, J., Horn, M., Vo Van, T., Seifert, G., Serchov, T., Biber, K., Nissen, C., Klugbauer, N., Bischofberger, J. (2018). Antidepressants protect synaptic plasticity from the effects of stress by inhibition of L-type Ca2+-channels. Biol Psychiatry, 84(1), 55-64.
5. Mallmann, R. T., Wilmes, T., Lichvarova, L., Bührer, A., Lohmüller, B., Castonguay, J., Lacinova, L., Klugbauer, N. (2013). Tetraspanin-13 modulates voltage-gated Cav2.2 Ca2+ channels. Sci Rep, 3, 1777, 1-8.
6. Mallmann, R. T., Elgueta, C., Sleman, F., Castonguay, J., Wilmes, T., van den Maagdenberg, A., Klugbauer, N. (2013). Ablation of Cav2.1 Voltage-Gated Ca2+ Channels in Mouse Forebrain Generates Multiple Cognitive Impairments. PLoS One, 8(10), e78598, 1-12.

Cav channels


II. Two-pore channels (TPCs)

Two-pore channels are a small family of intracellular unselective cation channels, that are gated by the second messenger NAADP and by PI(3,5)P2. This channels play an important role for intracellular trafficking. In previous studies, we investigated the precise localization of TPC1 within the endolysosomal system and its role for the uptake and processing of bacterial protein toxins. Currently, we are expanding our efforts to uncover the general role of TPCs for membrane receptor internalization, processing, degradation and recycling. In collaborative projects, we are investigating the physiological roles of TPC1 in brain and in kidney.

Key Papers:
1. Müller T, Grossmann S, Mallmann RT, Rommel C, Hein L, Klugbauer N (2021) Two-pore channels affect EGF receptor signaling by receptor trafficking and expression. iScience, 24, 1-30.

2. Mallmann RT, Klugbauer N (2020) Genetic Inactivation of Two-Pore Channel 1 Impairs Spatial Learning and Memory. Behav Genet, 50, 401-410. 3. Arlt E, Fraticelli M, Tsvilovskyy V, Nadolni W, Breit A, O'Neill TJ, Resenberger S, Wennemuth G, Wahl-Schott C, Biel M, Grimm C, Freichel M, Gudermann T, Klugbauer N, Boekhoff I, Zierler S. (2020) TPC1 deficiency or blockade augments systemic anaphylaxis and mast cell activity. Proc Natl Acad Sci U S A, 117, 18068-18078.
4. Castonguay, J., Orth, J. H. C., Müller, T., Sleman, F., Grimm, C., Wahl-Schott, C., Biel, M., Mallmann, R. T., Bildl, W., Schulte, U., Klugbauer, N. (2017). The two-pore channel TPC1 is required for efficient protein processing through early and recycling endosomes. Sci Rep, 7, 10038, 1-15.
5. Sakurai, Y., Kolokoltsov, A. A., Chen, C. C., Tidwell, M. W., Bauta, W. E., Klugbauer, N., Grimm, C., Wahl-Schott, C., Biel, M., Davey, R. A. (2015). Two-pore channels control Ebola virus host cell entry and are drug targets for disease treatment. Science, 347(6225), 995-998.
6. Grimm, C., Holdt, L. M., Chen, C. C., Hassan, S., Müller, C., Jörs, S., Cuny, H., Kissing, S., Schröder, B., Butz, E., Northoff, B., Castonguay, J., Luber, C. A., Moser, M., Spahn, S., Lüllmann-Rauch, R., Fendel, C., Klugbauer, N., Griesbeck, O., Haas, A., Mann, M., Bracher, F., Teupser, D., Saftig, P., Biel, M., Wahl-Schott, C. (2014). High susceptibility to fatty liver disease in two-pore channel 2-deficient mice. Nat Commun, 5, 4699, 1-13.