Kaupp U. Benjamin

No Thumbnail Available
Last Name
Kaupp
First Name
U. Benjamin
ORCID

Filters

2004 - 2009 1 2010 - 2020 5
6
6
Reset filters

Settings

Search Results

Now showing 1 - 6 of 6
  • Article
    Author correction: the solute carrier SLC9C1 is a Na(+)/H(+)-exchanger gated by an S4-type voltage-sensor and cyclic-nucleotide binding
    (Nature Research, 2020-08-19) Windler, Florian ; Bönigk, Wolfgang ; Körschen, Heinz Gerd ; Grahn, Elena ; Strünker, Timo ; Seifert, Reinhard ; Kaupp, U. Benjamin
  • Article
    The solute carrier SLC9C1 is a Na+/H+-exchanger gated by an S4-type voltage-sensor and cyclic-nucleotide binding
    (Nature Publishing Group, 2018-07-18) Windler, Florian ; Bönigk, Wolfgang ; Körschen, Heinz Gerd ; Grahn, Elena ; Strünker, Timo ; Seifert, Reinhard ; Kaupp, U. Benjamin
    Voltage-sensing (VSD) and cyclic nucleotide-binding domains (CNBD) gate ion channels for rapid electrical signaling. By contrast, solute carriers (SLCs) that passively redistribute substrates are gated by their substrates themselves. Here, we study the orphan sperm-specific solute carriers SLC9C1 that feature a unique tripartite structure: an exchanger domain, a VSD, and a CNBD. Voltage-clamp fluorimetry shows that SLC9C1 is a genuine Na+/H+ exchanger gated by voltage. The cellular messenger cAMP shifts the voltage range of activation. Mutations in the transport domain, the VSD, or the CNBD strongly affect Na+/H+ exchange, voltage gating, or cAMP sensitivity, respectively. Our results establish SLC9C1 as a phylogenetic chimaera that combines the ion-exchange mechanism of solute carriers with the gating mechanism of ion channels. Classic SLCs slowly readjust changes in the intra- and extracellular milieu, whereas voltage gating endows the Na+/H+ exchanger with the ability to produce a rapid pH response that enables downstream signaling events.
  • Article
    Revisiting the role of H+ in chemotactic signaling of sperm
    (Rockefeller University Press, 2004-07-26) Solzin, Johannes ; Helbig, Annika ; Van, Qui ; Brown, Joel E. ; Hildebrand, Eilo ; Weyand, Ingo ; Kaupp, U. Benjamin
    Chemotaxis of sperm is an important step toward fertilization. During chemotaxis, sperm change their swimming behavior in a gradient of the chemoattractant that is released by the eggs, and finally sperm accumulate near the eggs. A well established model to study chemotaxis is the sea urchin Arbacia punctulata. Resact, the chemoattractant of Arbacia, is a peptide that binds to a receptor guanylyl cyclase. The signaling pathway underlying chemotaxis is still poorly understood. Stimulation of sperm with resact induces a variety of cellular events, including a rise in intracellular pH (pHi) and an influx of Ca2+; the Ca2+ entry is essential for the chemotactic behavior. Previous studies proposed that the influx of Ca2+ is initiated by the rise in pHi. According to this proposal, a cGMP-induced hyperpolarization activates a voltage-dependent Na+/H+ exchanger that expels H+ from the cell. Because some aspects of the proposed signaling pathway are inconsistent with recent results (Kaupp, U.B., J. Solzin, J.E. Brown, A. Helbig, V. Hagen, M. Beyermann, E. Hildebrand, and I. Weyand. 2003. Nat. Cell Biol. 5:109–117), we reexamined the role of protons in chemotaxis of sperm using kinetic measurements of the changes in pHi and intracellular Ca2+ concentration. We show that for physiological concentrations of resact (<25 pM), the influx of Ca2+ precedes the rise in pHi. Moreover, buffering of pHi completely abolishes the resact-induced pHi signal, but leaves the Ca2+ signal and the chemotactic motor response unaffected. We conclude that an elevation of pHi is required neither to open Ca2+-permeable channels nor to control the chemotactic behavior. Intracellular release of cGMP from a caged compound does not cause an increase in pHi, indicating that the rise in pHi is induced by cellular events unrelated to cGMP itself, but probably triggered by the consumption and subsequent replenishment of GTP. These results show that the resact-induced rise in pHi is not an obligatory step in sperm chemotactic signaling. A rise in pHi is also not required for peptide-induced Ca2+ entry into sperm of the sea urchin Strongylocentrotus purpuratus. Speract, a peptide of S. purpuratus may act as a chemoattractant as well or may serve functions other than chemotaxis.
  • Article
    Temporal sampling, resetting, and adaptation orchestrate gradient sensing in sperm
    (Rockefeller University Press, 2012-09-17) Kashikar, Nachiket D. ; Alvarez, Luis ; Seifert, Reinhard ; Gregor, Ingo ; Jackle, Oliver ; Beyermann, Michael ; Krause, Eberhard ; Kaupp, U. Benjamin
    Sperm, navigating in a chemical gradient, are exposed to a periodic stream of chemoattractant molecules. The periodic stimulation entrains Ca2+ oscillations that control looping steering responses. It is not known how sperm sample chemoattractant molecules during periodic stimulation and adjust their sensitivity. We report that sea urchin sperm sampled molecules for 0.2–0.6 s before a Ca2+ response was produced. Additional molecules delivered during a Ca2+ response reset the cell by causing a pronounced Ca2+ drop that terminated the response; this reset was followed by a new Ca2+ rise. After stimulation, sperm adapted their sensitivity following the Weber–Fechner law. Taking into account the single-molecule sensitivity, we estimate that sperm can register a minimal gradient of 0.8 fM/µm and be attracted from as far away as 4.7 mm. Many microorganisms sense stimulus gradients along periodic paths to translate a spatial distribution of the stimulus into a temporal pattern of the cell response. Orchestration of temporal sampling, resetting, and adaptation might control gradient sensing in such organisms as well.
  • Article
    High density and ligand affinity confer ultrasensitive signal detection by a guanylyl cyclase chemoreceptor
    (Rockefeller University Press, 2014-08-18) Pichlo, Magdalena ; Bungert-Plumke, Stefanie ; Weyand, Ingo ; Seifert, Reinhard ; Bonigk, Wolfgang ; Strunker, Timo ; Kashikar, Nachiket D. ; Goodwin, Normann ; Muller, Astrid ; Pelzer, Patric ; Van, Qui ; Enderlein, Jorg ; Klemm, Clementine ; Krause, Eberhard ; Trotschel, Christian ; Poetsch, Ansgar ; Kremmer, Elisabeth ; Kaupp, U. Benjamin
    Guanylyl cyclases (GCs), which synthesize the messenger cyclic guanosine 3′,5′-monophosphate, control several sensory functions, such as phototransduction, chemosensation, and thermosensation, in many species from worms to mammals. The GC chemoreceptor in sea urchin sperm can decode chemoattractant concentrations with single-molecule sensitivity. The molecular and cellular underpinnings of such ultrasensitivity are not known for any eukaryotic chemoreceptor. In this paper, we show that an exquisitely high density of 3 × 105 GC chemoreceptors and subnanomolar ligand affinity provide a high ligand-capture efficacy and render sperm perfect absorbers. The GC activity is terminated within 150 ms by dephosphorylation steps of the receptor, which provides a means for precise control of the GC lifetime and which reduces “molecule noise.” Compared with other ultrasensitive sensory systems, the 10-fold signal amplification by the GC receptor is surprisingly low. The hallmarks of this signaling mechanism provide a blueprint for chemical sensing in small compartments, such as olfactory cilia, insect antennae, or even synaptic boutons.
  • Article
    Absolute proteomic quantification reveals design principles of sperm flagellar chemosensation
    (EMBO Press, 2019-12-27) Trotschel, Christian ; Hamzeh, Hussein ; Alvarez, Luis ; Pascal, René ; Lavryk, Fedir ; Bönigk, Wolfgang ; Körschen, Heinz Gerd ; Müller, Astrid ; Poetsch, Ansgar ; Rennhack, Andreas ; Gui, Long ; Nicastro, Daniela ; Strünker, Timo ; Seifert, Reinhard ; Kaupp, U. Benjamin
    Cilia serve as cellular antennae that translate sensory information into physiological responses. In the sperm flagellum, a single chemoattractant molecule can trigger a Ca2+ rise that controls motility. The mechanisms underlying such ultra‐sensitivity are ill‐defined. Here, we determine by mass spectrometry the copy number of nineteen chemosensory signaling proteins in sperm flagella from the sea urchin Arbacia punctulata. Proteins are up to 1,000‐fold more abundant than the free cellular messengers cAMP, cGMP, H+, and Ca2+. Opto‐chemical techniques show that high protein concentrations kinetically compartmentalize the flagellum: Within milliseconds, cGMP is relayed from the receptor guanylate cyclase to a cGMP‐gated channel that serves as a perfect chemo‐electrical transducer. cGMP is rapidly hydrolyzed, possibly via “substrate channeling” from the channel to the phosphodiesterase PDE5. The channel/PDE5 tandem encodes cGMP turnover rates rather than concentrations. The rate‐detection mechanism allows continuous stimulus sampling over a wide dynamic range. The textbook notion of signal amplification—few enzyme molecules process many messenger molecules—does not hold for sperm flagella. Instead, high protein concentrations ascertain messenger detection. Similar mechanisms may occur in other small compartments like primary cilia or dendritic spines.