Biology subjects

Kataoka, N.

Publications and source records attributed to Kataoka, N..

6 recordsLinked to original sources

bioRxiv2026

MDS-causing mutations of ZRSR2 impair minor intron splicing by reducing its interaction with SF3B complex

Minor introns are rare but evolutionarily conserved introns in the human genome. Defects in minor spliceosome components have been reported to cause several human diseases. Mutations in ZRSR2 are frequently observed in myelodysplastic syndrome (MDS) patients. However, the precise molecular mechanism by which these mutations cause a loss of ZRSR2 function in minor intron splicing remain elusive. In this study, we characterized the impact of MDS-causing missense mutations in ZRSR2. Most of the mutant ZRSR2 proteins we tested showed different subnuclear localization pattern from that of wild-type ZRSR2 protein. Co-immunoprecipitation (co-IP) analysis revealed that UHM missense mutations disrupted the interaction between ZRSR2 and SF3B complex. We also demonstrated that ZRSR2 preferentially immunoprecipitated minor spliceosome components over major spliceosome components and it directly interacts with SF3B1. Furthermore, co-IP analysis utilizing a variety of ZRSR2 mutants revealed that mutations in the UHM and Zn2 domains significantly attenuated the interaction with SF3B complex. Finally, UHM and Zn2 mutations markedly disrupted the supporting activity of ZRSR2 for minor intron splicing. Our results indicate that disruption of the physical interaction with SF3B complex is one of the hallmarks of MDS-causing mutations of ZRSR2, which results in aberrant splicing of minor introns.

molecular biology↗

bioRxiv2025

Deep-brain thermo-endomicroscopy

Subtle deviations in biophysical parameters, particularly temperature, within deep-brain regions exert substantial effects on whole-body homeostasis and metabolism. However, the underlying mechanisms remain poorly understood because cellular-resolution measurements of these parameters in the deep brain have been technically inaccessible. Here, we present a lensless fiber-optic quantum-sensing endomicroscopy that enables cellular-resolution temperature mapping in the mouse deep brain. A microwire-coupled, lensless fiber bundle permits simultaneous temperature readout from optically detected magnetic resonance spectra of >50 fluorescent nanodiamonds, achieving cellular resolution (4.88 m) with a precision of 0.49 (minimum precision, 0.18 ) within a 0.28 mm2 field of view. We demonstrated temperature mapping of multiple brain depths in head-fixed and vigorously behaving mice subjected to nociceptive stimulation, detecting lower temperatures during anesthesia compared to the awake state in ventromedial hypothalamic nucleus (VMH) at a 5 mm depth. These mappings reveal that spatio-temporal temperature distribution and its anesthesia-dependent reduction are heterogeneous rather than uniform in VMH. This endomicroscopy provides a promising platform to dissect how deviations in biophysical parameters modulate deep-brain function.

biophysics↗

bioRxiv2023

Study on Vibrational Behavior of Cytoskeletons Modeled by Cylindrical Tensegrity Structure

The dynamic mechanism of a cellular cytoskeleton is essential for the role of the cell, and its accurate characterization has been a long-standing problem for cell scientists. A cytoskeletons vibrations are highly influenced by interactions of filamentous proteins mediated by axial vibration of the stiff microtubules (compressive member) and lateral vibration of F-actin (tensile member). Among various structures in a cell, the cytoplasmic contractile bundles, lamellipodia, and filipodia cells can be modeled by a symmetrical cylinder-shaped self-equilibrium tensegrity structure with different radii at the top and bottom of the cylinder. The truncated conelike cylinder model is made to be small in height compared to both radii. This study investigates the tensegrity self-vibrational behavior of the cellular cytoskeleton to calculate its natural frequencies, composed of the individual vibration of microtubules and F-actins from measured data. The spectral element method is adopted based on the Wittrick-Williams procedure to solve the vibrational behaviors of the cellular cytoskeleton. Various n-polygon cylindrical truncated cone-shaped tensegrity structures to mimic the cellular cytoskeletons are presented to demonstrate the robustness of the present study.

cell biology↗

bioRxiv2023

Two Ascending Thermosensory Pathways from the Lateral Parabrachial Nucleus That Mediate Behavioral and Autonomous Thermoregulation

Thermoregulatory behavior in homeothermic animals is an innate behavior to defend body core temperature from environmental thermal challenges in coordination with autonomous thermoregulatory responses. In contrast to the progress in understanding the central mechanisms of autonomous thermoregulation, those of behavioral thermoregulation remain poorly understood. We have previously shown that the lateral parabrachial nucleus (LPB) mediates cutaneous thermosensory afferent signaling for thermoregulation. To understand the thermosensory neural network for behavioral thermoregulation, in the present study, we investigated the roles of ascending thermosensory pathways from the LPB in avoidance behavior from innocuous heat and cold in rats. Neuronal tracing revealed two segregated groups of LPB neurons projecting to the median preoptic nucleus (MnPO), a thermoregulatory center (LPB[->]MnPO neurons), and those projecting to the central amygdaloid nucleus (CeA), a limbic emotion center (LPB[->]CeA neurons). While LPB[->]MnPO neurons include separate subgroups activated by heat or cold exposure of rats, LPB[->]CeA neurons were only activated by cold exposure. By selectively inhibiting LPB[->]MnPO or LPB[->]CeA neurons using tetanus toxin light chain or chemogenetic or optogenetic techniques, we found that LPB[->]MnPO transmission mediates heat avoidance, whereas LPB[->]CeA transmission contributes to cold avoidance. In vivo electrophysiological experiments showed that skin cooling-evoked thermogenesis in brown adipose tissue requires not only LPB[->]MnPO neurons but also LPB[->]CeA neurons, providing a novel insight into the central mechanism of autonomous thermoregulation. Our findings reveal an important framework of central thermosensory afferent pathways to coordinate behavioral and autonomous thermoregulation and to generate the emotions of thermal comfort and discomfort that drive thermoregulatory behavior.

neuroscience↗

bioRxiv2022

Prostaglandin EP3 receptor-expressing preoptic neurons bidirectionally control body temperature via tonic GABAergic signaling

The circuit mechanism of the thermoregulatory center in the preoptic area (POA) is unknown. Using rats, here we show prostaglandin EP3 receptor-expressing POA neurons (POAEP3R neurons) as a pivotal bidirectional controller in the central thermoregulatory mechanism. POAEP3R neurons are activated in response to elevated ambient temperature, but inhibited by prostaglandin E2, a pyrogenic mediator. Chemogenetic stimulation of POAEP3R neurons at room temperature reduces body temperature by enhancing heat dissipation, whereas inhibition of them elicits hyperthermia involving brown fat thermogenesis, mimicking fever. POAEP3R neurons innervate sympathoexcitatory neurons in the dorsomedial hypothalamus (DMH) via tonic inhibitory signaling. Although many POAEP3R neuronal cell bodies express a glutamatergic mRNA marker, paradoxically, their axons in the DMH predominantly contain terminals with GABAergic presynaptic proteins, which are increased by chronic heat exposure. These findings indicate that tonic GABAergic inhibitory signaling from POAEP3R neurons is a fundamental determinant of body temperature for thermal homeostasis and fever.

physiology↗

bioRxiv2021

Metabolic flexibility via mitochondrial BCAA carrier SLC25A44 is required for optimal fever

Importing necessary metabolites into the mitochondrial matrix is a crucial step of fuel choice during stress adaptation. Branched chain-amino acids (BCAA, Valine, Leucine, and Isoleucine) are essential for anabolic processes like protein synthesis, but they are also imported into the mitochondria for catabolic reactions. What controls the distinct subcellular BCAA utilization during stress adaptation is insufficiently understood. The present study reports the role of SLC25A44, a recently identified mitochondrial BCAA carrier (MBC), in the regulation of mitochondrial BCAA catabolism and adaptive response to fever. We found that mitochondrial BCAA oxidation in brown adipose tissue (BAT) is significantly enhanced during fever in response to the pyrogenic mediator prostaglandin E2 (PGE2) and psychological stress. Genetic deletion of MBC in a BAT-specific manner blunts mitochondrial BCAA oxidation and non-shivering thermogenesis following intracerebroventricular PGE2 administration. At a cellular level, MBC is required for mitochondrial BCAA deamination as well as the synthesis of mitochondrial amino acids and TCA intermediates. Together, these results illuminate the role of MBC as a determinant of metabolic flexibility to mitochondrial BCAA catabolism and optimal febrile responses. This study also offers an opportunity to control fever by rewiring the subcellular BCAA fate.

cell biology↗