17 research outputs found
Piezo1-pannexin-1-P2X3 axis in odontoblasts and neurons mediates sensory transduction in dentinal sensitivity
©2022 Ohyama, Ouchi, Kimura, Kurashima, Yasumatsu, Nishida, Hitomi, Ubaidus, Kuroda, Ito, Takano, Ono, Mizoguchi, Katakura and Shibukawa. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms
A new family of periplasmic-binding proteins that sense arsenic oxyanions
Arsenic contamination of drinking water affects more than 140 million people worldwide. While toxic to humans, inorganic forms of arsenic (arsenite and arsenate), can be used as energy sources for microbial respiration. AioX and its orthologues (ArxX and ArrX) represent the first members of a new sub-family of periplasmic-binding proteins that serve as the first component of a signal transduction system, that's role is to positively regulate expression of arsenic metabolism enzymes. As determined by X-ray crystallography for AioX, arsenite binding only requires subtle conformational changes in protein structure, providing insights into protein-ligand interactions. The binding pocket of all orthologues is conserved but this alone is not sufficient for oxyanion selectivity, with proteins selectively binding either arsenite or arsenate. Phylogenetic evidence, clearly demonstrates that the regulatory proteins evolved together early in prokaryotic evolution and had a separate origin from the metabolic enzymes whose expression they regulate
Left−Right Asymmetry Defect in the Hippocampal Circuitry Impairs Spatial Learning and Working Memory in iv Mice
Although left-right (L−R) asymmetry is a fundamental feature of higher-order brain function, little is known about how asymmetry defects of the brain affect animal behavior. Previously, we identified structural and functional asymmetries in the circuitry of the mouse hippocampus resulting from the asymmetrical distribution of NMDA receptor GluR ε2 (NR2B) subunits. We further examined the ε2 asymmetry in the inversus viscerum (iv) mouse, which has randomized laterality of internal organs, and found that the iv mouse hippocampus exhibits right isomerism (bilateral right-sidedness) in the synaptic distribution of theε2 subunit, irrespective of the laterality of visceral organs. To investigate the effects of hippocampal laterality defects on higher-order brain functions, we examined the capacity of reference and working memories of iv mice using a dry maze and a delayed nonmatching-to-position (DNMTP) task, respectively. The iv mice improved dry maze performance more slowly than control mice during acquisition, whereas the asymptotic level of performance was similar between the two groups. In the DNMTP task, the iv mice showed poorer accuracy than control mice as the retention interval became longer. These results suggest that the L−R asymmetry of hippocampal circuitry is critical for the acquisition of reference memory and the retention of working memory
Structural and Functional Analysis of the C-terminal DNA Binding Domain of the Salmonella typhimurium SPI-2 Response Regulator SsrB*S⃞
In bacterial pathogenesis, virulence gene regulation is controlled by
two-component regulatory systems. In Escherichia coli, the EnvZ/OmpR
two-component system is best understood as regulating expression of outer
membrane proteins, but in Salmonella enterica, OmpR activates
transcription of the SsrA/B two-component system located on
Salmonella pathogenicity island 2 (SPI-2). The response regulator
SsrB controls expression of a type III secretory system in which effectors
modify the vacuolar membrane and prevent its degradation via the endocytic
pathway. Vacuolar modification enables Salmonella to survive and
replicate in the macrophage phagosome and disseminate to the liver and spleen
to cause systemic infection. The signals that activate EnvZ and SsrA are
unknown but are related to the acidic pH encountered in the vacuole. Our
previous work established that SsrB binds to regions of DNA that are AT-rich,
with poor sequence conservation. Although SsrB is a major virulence regulator
in Salmonella, very little is known regarding how it binds DNA and
activates transcription. In the present work, we solved the structure of the
C-terminal DNA binding domain of SsrB (SsrBC) by NMR and analyzed
the effect of amino acid substitutions on function. We identified residues in
the DNA recognition helix (Lys179, Met186) and the
dimerization interface (Val197, Leu201) that are
important for SsrB transcriptional activation and DNA binding. An essential
cysteine residue in the N-terminal receiver domain was also identified
(Cys45), and the effect of Cys203 on dimerization was
evaluated. Our results suggest that although disulfide bond formation is not
required for dimerization, dimerization occurs upon DNA binding and is
required for subsequent activation of transcription. Disruption of the dimer
interface by a C203E substitution reduces SsrB activity. Modification of
Cys203 or Cys45 may be an important mode of SsrB
inactivation inside the host