Browsing by Subject "signaling"

Now showing 1 - 4 of 4
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    Ca2+ channel nanodomains boost local Ca2+ amplitude.
    (Proc Natl Acad Sci U S A, 2013-09-24) Tadross, Michael R; Tsien, Richard W; Yue, David T
    Local Ca(2+) signals through voltage-gated Ca(2+) channels (CaVs) drive synaptic transmission, neural plasticity, and cardiac contraction. Despite the importance of these events, the fundamental relationship between flux through a single CaV channel and the Ca(2+) signaling concentration within nanometers of its pore has resisted empirical determination, owing to limitations in the spatial resolution and specificity of fluorescence-based Ca(2+) measurements. Here, we exploited Ca(2+)-dependent inactivation of CaV channels as a nanometer-range Ca(2+) indicator specific to active channels. We observed an unexpected and dramatic boost in nanodomain Ca(2+) amplitude, ten-fold higher than predicted on theoretical grounds. Our results uncover a striking feature of CaV nanodomains, as diffusion-restricted environments that amplify small Ca(2+) fluxes into enormous local Ca(2+) concentrations. This Ca(2+) tuning by the physical composition of the nanodomain may represent an energy-efficient means of local amplification that maximizes information signaling capacity, while minimizing global Ca(2+) load.
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    Phosphorylation of Human Tristetraprolin in Response to Its Interaction with the CbI Interacting Protein CIN85
    (2010) Kedar, Vishram P; Darby, Martyn K; Williams, Jason G; Blackshear, Perry J
    Background: Tristetraprolin (TTP) is the prototype member of a family of CCCH tandem zinc finger proteins and is considered to be an anti-inflammatory protein in mammals. TTP plays a critical role in the decay of tumor necrosis factor alpha (TNF) mRNA, among others, by binding AU-rich RNA elements in the 3'-untranslated regions of this transcript and promoting its deadenylation and degradation. Methodology/Principal Findings: We used yeast two-hybrid analysis to identify potential protein binding partners for human TTP (hTTP). Various regions of hTTP recovered 31 proteins that fell into 12 categories based on sequence similarities. Among these, the interactions between hTTP and CIN85, cytoplasmic poly (A) binding protein (PABP), nucleolin and heat shock protein 70 were confirmed by co-immunoprecipitation experiments. CIN85 and hTTP co-localized in the cytoplasm of cells as determined by confocal microscopy. CIN85 contains three SH3 domains that specifically bind a unique proline-arginine motif (PXXXPR) found in several CIN85 effectors. We found that the SH3 domains of CIN85 bound to a PXXXPR motif located near the C-terminus of hTTP. Co-expression of CIN85 with hTTP resulted in the increased phosphorylation of hTTP at serine residues in positions 66 and 93, possibly due in part to the demonstrated association of mitogen-activated protein kinase kinase kinase 4 (MEKK4) to both proteins. The presence of CIN85 did not appear to alter hTTP's binding to RNA probes or its stimulated breakdown of TNF mRNA. Conclusions/Significance: These studies describe interactions between hTTP and nucleolin, cytoplasmic PABP, heat shock protein 70 and CIN85; these interactions were initially discovered by two-hybrid analysis, and confirmed by coimmunoprecipitation. We found that CIN85 binding to a C-terminal motif within hTTP led to the increased phosphorylation of hTTP, possibly through enhanced association with MEKK4. The functional consequences to each of the members of this putative complex remain to be determined.
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    Sounds of senescence: Male swamp sparrows respond less aggressively to the songs of older individuals
    (Behavioral Ecology, 2021-01-01) Zipple, MN; Peters, S; Searcy, WA; Nowicki, S
    Age-related changes in assessment signals occur in a diverse array of animals, including humans. Age-related decline in vocal quality in humans is known to affect perceived attractiveness by potential mates and voters, but whether such changes have functional implications for nonhuman animals is poorly understood. Most studies of age-related change in animal signals focus on increases in signal quality that occur soon after the age of first breeding (“delayed maturation”), but a few have shown that signal quality declines in older individuals after a mid-life peak (“behavioral senescence”). Whether other individuals are able to detect this senescent decline of assessment signals has not previously been tested. Here we use playback experiments to show that wild male swamp sparrows (Melospiza georgiana) respond more aggressively to songs from 2-year-old males as compared with songs from the same males when they are 10 years old. Senescence in signals that, like birdsong, affect reproductive success through intrasexual competition or mate choice may be of evolutionary significance. Lay Summary: Using playback experiments with wild swamp sparrows (Melospiza georgiana), we demonstrate that listeners both detect and respond to age-related declines in vocal quality. Two previous studies have shown that some song characteristics deteriorate with age later in life in songbirds, but to our knowledge this is the first demonstration outside of humans that such deterioration affects receiver response. Discrimination of songs from males of different ages may have evolutionary implications.
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    The Physarum polycephalum Genome Reveals Extensive Use of Prokaryotic Two-Component and Metazoan-Type Tyrosine Kinase Signaling.
    (Genome Biol Evol, 2015-11-27) Schaap, Pauline; Barrantes, Israel; Minx, Pat; Sasaki, Narie; Anderson, Roger W; Bénard, Marianne; Biggar, Kyle K; Buchler, Nicolas E; Bundschuh, Ralf; Chen, Xiao; Fronick, Catrina; Fulton, Lucinda; Golderer, Georg; Jahn, Niels; Knoop, Volker; Landweber, Laura F; Maric, Chrystelle; Miller, Dennis; Noegel, Angelika A; Peace, Rob; Pierron, Gérard; Sasaki, Taeko; Schallenberg-Rüdinger, Mareike; Schleicher, Michael; Singh, Reema; Spaller, Thomas; Storey, Kenneth B; Suzuki, Takamasa; Tomlinson, Chad; Tyson, John J; Warren, Wesley C; Werner, Ernst R; Werner-Felmayer, Gabriele; Wilson, Richard K; Winckler, Thomas; Gott, Jonatha M; Glöckner, Gernot; Marwan, Wolfgang
    Physarum polycephalum is a well-studied microbial eukaryote with unique experimental attributes relative to other experimental model organisms. It has a sophisticated life cycle with several distinct stages including amoebal, flagellated, and plasmodial cells. It is unusual in switching between open and closed mitosis according to specific life-cycle stages. Here we present the analysis of the genome of this enigmatic and important model organism and compare it with closely related species. The genome is littered with simple and complex repeats and the coding regions are frequently interrupted by introns with a mean size of 100 bases. Complemented with extensive transcriptome data, we define approximately 31,000 gene loci, providing unexpected insights into early eukaryote evolution. We describe extensive use of histidine kinase-based two-component systems and tyrosine kinase signaling, the presence of bacterial and plant type photoreceptors (phytochromes, cryptochrome, and phototropin) and of plant-type pentatricopeptide repeat proteins, as well as metabolic pathways, and a cell cycle control system typically found in more complex eukaryotes. Our analysis characterizes P. polycephalum as a prototypical eukaryote with features attributed to the last common ancestor of Amorphea, that is, the Amoebozoa and Opisthokonts. Specifically, the presence of tyrosine kinases in Acanthamoeba and Physarum as representatives of two distantly related subdivisions of Amoebozoa argues against the later emergence of tyrosine kinase signaling in the opisthokont lineage and also against the acquisition by horizontal gene transfer.