Kashikar Nachiket D.

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Kashikar
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Nachiket D.
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  • 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.