Biophysics of Ion Channels

My research activities focus on the biophysics of ion channels. Ion channels are membrane proteins that determine the electrical activity of cells. A number of questions are particularly interesting: What are the molecular determinants for ion selectivity? What is the nature of the conformational changes that take place during activation of an ion channel? What is the function of an ion channel in its physiological context?

We are studying these questions using ion channels that are regulated by cyclic nucleotides. These channels have important roles in sensory transduction, in sperm physiology, and in the generation of rhythmic activity in neurons and in cardiac tissue. We are studying these channels using electrophysiological, optical, biochemical, and structural methods.

Publications

Hamzeh, H., Alvarez, L., Strünker, T., Kierzek, M., Brenker, C., Deal, P.E., Miller, E.W., Seifert, R., and Kaupp, U.B. (2019). Kinetic and photonic techniques to study chemotactic signaling in sea urchin sperm. Methods Cell Biol. 151, 487–517.

Schumacher, C.H., Körschen, H.G., Nicol, C., Gasser, C., Seifert, R., Schwarzel, M. & Moglich, A. (2016) "A Fluorometric Activity Assay for Light-Regulated Cyclic-Nucleotide-Monophosphate Actuators" Methods Mol. Biol. 1408, 93-105

Mukherjee, S., Jansen, V., Jikeli, J.F., Hamzeh, H., Alvarez, L., Dombrowski, M., Balbach, M., Strünker, T., Seifert, R. & Kaupp, U.B. (2016) "A novel biosensor to study cAMP dynamics in cilia and flagella" eLife 5, e14052

Fechner, S., Alvarez, L., Bönigk, W., Müller, A., Berger, T., Pascal, R., Trötschel, C., Poetsch, A., Stölting, G., Siegfried, K.R., Seifert, R. & Kaupp, U.B. (2015) "A K+-selective CNG channel orchestrates Ca2+ signalling in zebrafish sperm" eLife, e07624

Seifert, R., Flick, M., Bönigk, W., Alvarez, L., Trötschel, C., Poetsch, A., Müller, A., Goodwin, N., Pelzer, P., Kashikar, N.D., Kremmer, E., Jikeli, J., Timmermann, B., Kuhl, H., Fridman, D., Windler, F., Kaupp, U.B. & Strünker, T. (2015) "The CatSper channel controls chemosensation in sea urchin sperm" EMBO J. 34, 379-392

Pichlo, M., Bungert-Plümke, S., Weyand, I., Seifert, R., Bönigk, W., Strünker, T., Kashikar, N.D., Goodwin, N., Müller, A., Pelzer, P., Van, Q., Enderlein, J., Klemm, C., Krause, E., Trotschel, C., Poetsch, A., Kremmer, E. & Kaupp, U.B. (2014) "High density and ligand affinity confer ultrasensitive signal detection by a guanylyl cyclase chemoreceptor" J. Cell. Biol. 206, 541-557

Geißler, K.J., Jung, M.J., Riecken, L.B., Sperka, T., Cui, Y., Schacke, S., Merkel, U., Markwart, R., Rubio, I., Than, M.E., Breithaupt, C., Peuker, S., Seifert, R., Kaupp, U.B., Herrlich, P. & Morrison, H. (2013) "Regulation of Son of sevenless by the membrane-actin linker protein ezrin" Proc. Natl. Acad. Sci. USA 110, 20587-20592

Krähling, M., Alvarez, L., Debowski, K., Van, Q., Gunkel, M., Irsen, S., Al-Amoudi, A., Strünker, T., Kremmer, E., Krause, E., Voigt, I., Wörtge, S., Waisman, A., Weyand, I., Seifert, R., Kaupp, U.B. & Wachten, D. (2013) "CRIS- a novel cAMP-binding protein controlling spermiogenesis and the development of flagellar bending" PLoS Genetics, e1003960

Peuker, S., Cukkemane, A., Held, M., Noé, F., Kaupp, U. B. & Seifert, R. (2013)"Kinetics of ligand-receptor interaction reveals an induced-fit mode of binding in a cyclic nucleotide-activated protein" Biophys. J. 104, 63-74

Kashikar, N. D., Alvarez, L., Seifert, R., Gregor, I., Jäckle, O., Beyermann, M., Krause, E. & Kaupp, U. B. (2012) "Temporal sampling, resetting, and adaptation orchestrate gradient sensing in sperm" J. Cell Biol. 198, 1075-1091

Nache, V., Zimmer, T., Wongsamitkul, N., Schmauder, R., Kusch, J., Reinhardt, L., Bönigk, W., Seifert, R., Biskup, C., Schwede, F. & Benndorf, K. (2012) "Differential regulation by cyclic nucleotides of the CNGA4 and CNGB1b subunits in olfactory cyclic nucleotide-gated channels" Sci Signal. 5, ra48

Kusch, J., Thon, S., Schulz, E., Biskup, C., Nache, V., Zimmer, T., Seifert, R., Schwede, F. & Benndorf, K. (2011) "How subunits cooperate in cAMP-induces activation of homotetrameric HCN2 channels" Nat. Chem. Biol. 8, 162-169

Strünker, T., Goodwin, N., Brenker, C., Kashikar, N.D., Weyand, I., Seifert, R. & Kaupp, U.B. (2011) "The CatSper channel mediates progesterone-induced Ca2+ influx in human sperm" Nature 471, 382-386

Bönigk, W., Loogen, A., Seifert, R., Kashikar, N., Klemm, C., Krause, E., Hagen, V., Kremmer, E., Strünker, T. & Kaupp, U.B. (2009) "An atypical CNG channel activated by a single cGMP molecule controls sperm chemotaxis" Sci. Signal. 2, ra68

Harzheim, D., Seifert, R., Pfeiffer, K.H., Fabritz, L., Kremmer, E., Buch, T., Waisman, A., Kirchhof, P. & Kaupp, U.B. (2008) "Cardiac pacemaker function of HCN4 channels is confined to embryonic development and requires cyclic AMP" EMBO J. 27, 692-703

Cukkemane, A., Grüter, B., Novak, K., Gensch, T., Bönigk, W., Gerharz, T., Kaupp, U.B. & Seifert, R. (2007) "Subunits act independently in a cyclic nucleotide-activated K+ channel" EMBO Reports 8, 749-755

Schröder-Lang, S., Schwärzel, M., Seifert, R., Strünker, T., Kateriya, S., Looser, J., Watanabe, M., Kaupp, U.B., Hegemann, P. & Nagel, G. (2007) "Fast manipulation of cellular cAMP level by light in vivo" Nat. Methods 4, 39-42

Wrobel, G., Seifert, R., Ingebrandt, S., Enderlein, J., Ecken, H., Baumann, A., Kaupp, U.B. & Offenhausser, A. (2005) "Cell-transistor coupling: investigation of potassium currents recorded with p- and n-channel FETs" Biophy. J. 89, 3628-3638

Tränkner, D., Jägle, H., Kohl, S., Apfelstedt-Sylla, E., Sharpe, L.T., Kaupp, U.B., Zrenner, E., Seifert, R. & Wissinger, B. (2004) "Molecular Basis of an Inherited Form of Incomplete Achromatopsia" J. Neurosci. 24, 138-147

Stevens, D.R., Seifert, R., Bufe, B., Muller, F., Kremmer, E., Gauss, R., Meyerhof. W., Kaupp, U.B., and Lindemann, B. (2001) "Hyperpolarization-activated channels HCN1 and HCN4 mediate responses to sour stimuli" Nature 413, 631-635

Seifert, R., Scholten, A., Gauss, R., Mincheva, A., Lichter, P. & Kaupp, U.B. (1999)"Molecular characterization of a slowly gating human hyperpolarization-activated channel predominantly expressed in thalamus, heart, and testis" Proc. Natl. Acad. Sci USA 96, 9391-9396

Seifert, R., Eismann, E., Ludwig, J., Baumann, A. & Kaupp, U.B. (1999) "Molecular determinants of a Ca2+-binding site in the pore of cyclic nucleotide-gated channels: S5/S6 segments control affinity of intrapore glutamates" EMBO J. 18, 119-130

Gauss, R., Seifert, R., Godde, M. & Kaupp, U.B. (1998) "Molecular identification of a hyperpolarization-activated channel in sea urchin sperm" Nature 393, 583-587

Frings, S., Seifert, R., Godde, M. & Kaupp, U.B. (1995) "Profoundly different calcium permeation and blockage determine the specific function of distinct cyclic nucleotide-gated channels" Neuron 15, 169-179

Körschen, H.G., Illing, M., Seifert, R., Sesti, F., Williams, A., Gotzes, S., Colville, C., Müller, F., Dose, A., Gödde, M., Molday, L., Kaupp, U.B. & Molday, R.S. (1995) "A 240 kDa protein represents the complete ? subunit of the cyclic nucleotide-gated channel from rod photoreceptor" Neuron 15, 627-636

Baumann, A., Frings, S., Godde, M., Seifert, R. & Kaupp, U.B. (1994) "Primary structure and functional expression of a Drosophila cyclic nucleotide-gated channel present in eyes and antennae" EMBO J. 13, 5040-5050

Reviews

Cukkemane, A., Seifert, R., and Kaupp, U.B. (2010) "Cooperative and uncooperative cyclic-nucleotide-gated ion channels" Trends Biochem Sci. 36, 55-64

Kaupp, U.B., and Seifert, R. (2002) "Cyclic nucleotide-gated ion channels" Physiol. Rev. 82, 769-824

Kaupp, U.B., and Seifert, R. (2001) "Molecular Diversity of Pacemaker Ion Channels"Annu. Rev. Physiol. 63, 235-257

Gauss, R., and Seifert, R. (2000) "Pacemaker osycillations in heart and brain: a key role for hyperpolarization-activated cation channels" Chronobiol. Int. 17, 453-569

Articles in books

Seifert, R. "Ion channels and pumps", in: Physics meets biology: from soft matter to cell biology; lecture notes of the 35th Spring School of the Institut für Festkörperforschung / eds.: Gompper, G., Kaupp, U.B., Dhont, J.K.G., Richter, D., Winkler, R.G., Jülich, Forschungszentrum (2004), S. D7.1 - D7.32

Teaching

University of Bonn

Neuroscience Master Course:

“Signal Transduction studied with dyes, light-driven proteins, and genetically encoded biosensors”