Biology subjects

Nishigaki, T.

Publications and source records attributed to Nishigaki, T..

5 recordsLinked to original sources

bioRxiv2025

A skeletal muscle-sympathetic nerve-intestine network underlies muscle inflammation and atrophy induced by immobilization

Immobility is a common cause of muscle atrophy, but the underlying mechanisms have remained unclear. Here we show that limb immobilization in mice elicits inflammation and atrophy of skeletal muscle that are preventable by neutralizing antibodies to the chemokine CXCL10. Limb immobilization also induced changes to the gut microbiota and intestinal inflammation, and either sterilization of the intestine with antibiotics or administration of 10-hydroxy-cis-12-octadecenoic acid--a linoleic acid-derived gut microbial metabolite--prevented intestinal and muscle inflammation as well as muscle atrophy induced by immobilization, implicating intestinal inflammation in muscle inflammation and atrophy. Limb immobilization activated sympathetic nerves and increased {beta}2-adrenergic receptor gene (Adrb2) expression in the intestine. Single-cell RNA-sequencing analysis revealed that, among cells expressing Adrb2 in the intestine, immobilization increased only the population of macrophages. Pharmacological inhibition or macrophage-specific ablation of Adrb2 prevented immobilization-induced intestinal and muscle inflammation. Our results thus implicate a previously unrecognized muscle-nerve-intestine network in immobilization-induced muscle atrophy.

molecular biology↗

bioRxiv2024

The sodium-proton exchangers sNHE and NHE1 control plasma membrane hyperpolarization in mouse sperm.

Sperm capacitation, crucial for fertilization, occurs in the female reproductive tract and can be replicated in vitro using a medium rich in bicarbonate, calcium, and albumin. These components trigger the cAMP-PKA signaling cascade, proposed to promote hyperpolarization of the mouse sperm plasma membrane through activation of SLO3 K+ channel. Hyperpolarization is a hallmark of capacitation: proper membrane hyperpolarization renders higher in vitro fertilizing ability, while Slo3 KO mice are infertile. However, the precise regulation of SLO3 opening remains elusive. Our study challenges the involvement of PKA in this event and reveals the role of Na+/H+ exchangers. During capacitation, calcium increase through CatSper channels activates NHE1, while cAMP directly stimulates the sperm-specific NHE, collectively promoting the alkalinization threshold needed for SLO3 opening. Hyperpolarization then feeds back Na+/H+ activity. Our work is supported by pharmacology, and a plethora of KO mouse models, and proposes a novel pathway leading to hyperpolarization. TeaserAlkalinization of sperm cytoplasm activates potassium channels to hyperpolarize the plasma membrane in a PKA independent cascade.

cell biology↗

bioRxiv2020

Synergy between a shallow root system with a DRO1 homologue and localized P application improves rice P uptake

The development of genotypes and fertilizer management practices that facilitate high phosphorus (P) use efficiency is needed given the depleting phosphorus ore deposits and increasing ecological concerns about its excessive use. Root system architecture (RSA) is important in efficiently capturing immobile P in soils, while agronomically, localized P application near the roots is a potential approach to address this issue. However, the interaction between genetic traits of RSA and localized P application has not been examined. Near-isogenic lines (NILs) and their parent of rice (qsor1-NIL, Dro1-NIL, and IR64, with shallow, deep, and intermediate root growth angles (RGA), respectively) were grown in flooded pots in a uniform and P-sufficient condition (Pinco), and with localized P application by dipping seedling roots into P-enriched slurry at transplanting (P-dipping). The P-dipping created an available P hotspot at the soil surface and substantially improved applied P-use efficiency (equivalent biomass at one fifth of application rate of the Pinco). Further, the qsor1-NIL had significantly greater biomass and P uptake than the other genotypes in the P-dipping. The qsor1-NIL consistently had a greater root biomass and surface area in the 0-3 cm soil layer, despite that there were no genotype differences in total values and that the other genotypes also reduced their RGAs responding to the P hotspot in the P-dipping. The shallow root system of qsor1-NIL facilitated P uptake from the P hotspot. P-use efficiency in crop production can be further increased by combining genetic traits of RSA and localized P application.

physiology↗

bioRxiv2019

CaV3.1 channel pore pseudo-symmetry revealed by selectivity filter mutations in their domains I/II

There is growing evidence indicating that the pore structure of voltage-gated ion channels (VGICs) influences gating besides their conductance. Regarding low voltage-activated (LVA) Ca2+ channels, it has been demonstrated that substitutions of the pore aspartate (D) by a glutamate (D-to-E substitution) in domains III and IV alter channel gating properties such as a positive shift in the channel activation voltage dependence. In the present report, we evaluated the effects of E-to-D substitution in domains I and II on the CaV3.1 channel gating properties. Our results indicate that substitutions in these two domains differentially modify the gating properties of CaV3.1 channels. The channel with a single mutation in domain I (DEDD) presented slower activation and faster inactivation kinetics and a slower recovery from inactivation, as compared with the WT channel. In contrast, the single mutant in domain II (EDDD) presented a small but significant negative shift of activation voltage dependence with faster activation and slower deactivation kinetics. Finally, the double mutant channel (DDDD) presented intermediate properties with respect to the two single mutants but with fastest deactivation kinetics. Overall, our results indicate that single amino acid modification of the selectivity filter of LVA Ca2+ channels in distinct domains differentially influence their gating properties, suggesting a pore pseudo-symmetry.\n\nStatement of significancePrevious reports of low voltage-activated (LVA) Ca2+ channels have demonstrated that pore aspartate (D) in domains III and IV equally modulates the channel gating properties, supporting a hypothesis of pore symmetry in LVA Ca2+ channels. In the present report, we evaluated the effects of glutamate (E)-to-D pore substitution in domains I and II on the CaV3.1 channel gating properties. Our results indicate that substitutions in these two domains differentially modify the gating properties of CaV3.1 channels, therefore suggesting a pore pseudo-symmetry in them. Interestingly, our pore mutations affect inactivation of CaV3.1 Ca2+ channels indicating a selectivity filter contribution to this process similar to the recent proposed paradigm for high voltage-activated Ca2+ channels.

biophysics↗

bioRxiv2018

Interplay scenarios between CatSper and CaV channels in sea urchin sperm flagellum signaling cascades triggered by egg peptides: a mathematical modelling approach

Intracellular calcium ([Ca2+]i) is a basic, versatile and ubiquitous cellular signal controlling a wide variety of biological processes. A remarkable example is the steering of sea urchin spermatozoa towards the conspecific egg by a spatially and temporally orchestrated series of cytosolic [Ca2+]i spikes. Although this process has been an experimental paradigm for reproduction and sperm chemotaxis studies, the composition and regulation of the signalling network underlying the cytosolic calcium fluctuations are hitherto not fully understood. Here, we used a differential equations model of the signalling network to assess which set of channels can explain the characteristic envelop and temporal organisation of the [Ca2+]i-spike trains. The signalling network comprises an initial membrane hyperpolarisation/repolarisation produced by an upstream module triggered by the egg-released chemoattractant peptide, via receptor activation, cGMP synthesis and decay. Followed by downstream modules leading to pHi, voltage and [Ca2+]i fluctuations. The upstream module outputs were fitted to kinetic data on cGMP activity and early membrane potential changes measured in bulk cell populations. Two candidate modules featuring voltage-dependent Ca2+-channels link these outputs to the downstream dynamics and can independently explain the typical decaying envelop and the progressive spacing of the spikes. In the first module, [Ca2+]i-spike trains require the concerted action of a classical CaV-like channel and a potassium channel, BK (Slo1), whereas the second module relies on pHi-dependent, [Ca2+]i-inactivated CatSper dynamics alone. The model predicts that these two modules interfere with each other and produce unreasonable dynamics when present at similar proportions, which suggests that one may predominate over the other in vivo. To assess these alternatives, several quantitative predictions were derived from each module and confronted to experimental observations. We show that the [Ca2+]I dynamics observed experimentally after sustained alkalinisation can be reproduced by a model featuring the CatSper module but not by one including the pH-independent CaV and BK module. We conclude in favour of the module containing CatSper.

developmental biology↗