A5011788979- Cellular transport and secretion
- Phagocytosis and Immune Regulation
- Erythrocyte Function and Pathophysiology
- Adenosine and Purinergic Signaling
- RNA Interference and Gene Delivery
- Planarian Biology and Electrostimulation
- Hematopoietic Stem Cell Transplantation
- Sexual function and dysfunction studies
- Immune Cell Function and Interaction
- Pancreatic function and diabetes
- Mitochondrial Function and Pathology
- Hormonal and reproductive studies
- Cancer, Hypoxia, and Metabolism
- Protein Kinase Regulation and GTPase Signaling
- Glycosylation and Glycoproteins Research
- Immune cells in cancer
- Shakespeare, Adaptation, and Literary Criticism
- Sexuality, Behavior, and Technology
- Trypanosoma species research and implications
- Calcium signaling and nucleotide metabolism
- Genomics and Chromatin Dynamics
- Multidisciplinary Warburg-centric Studies
- Sphingolipid Metabolism and Signaling
- Biochemical and Molecular Research
- Art, Politics, and Modernism
Tokyo Medical and Dental University
2019-2024
Kanazawa University
2023-2024
The University of Tokyo
2022
Hiroshima University
2014-2019
Abstract Phosphoinositides are a family of membrane lipids essential for many biological and pathological processes. Due to the existence multiple phosphoinositide regioisomers their low intracellular concentrations, profiling these linking specific acyl variant change in state have been difficult. To enable comprehensive analysis phosphorylation status chain identity, we develop PRMC-MS (Phosphoinositide Regioisomer Measurement by Chiral column chromatography Mass Spectrometry). Using this...
Nucleosome dynamics, such as nucleosome sliding and DNA unwrapping, are important for gene regulation in eukaryotic chromatin. H2A.Z, a variant of histone H2A that is highly evolutionarily conserved, participates by forming unstable multipositioned nucleosomes vivo vitro. However, the subsecond dynamics this have not been directly visualized under physiological conditions. Here, we used high-speed atomic force microscopy (HS-AFM) to visualize human H2A.Z.1-nucleosomes. HS-AFM videos show...
Each nucleosome contains four types of histone proteins, each with a tail. These tails are essential for the epigenetic regulation gene expression through post-translational modifications (PTMs). However, their influence on dynamics at single-molecule level remains undetermined. Here, we employed high-speed atomic force microscopy to visualize in absence N-terminal tail or all tails. Loss stripped 6.7 base pairs from core, and DNA entry-exit angle expanded by 18° that wild-type nucleosomes....
Significance Voltage-sensing phosphatase (VSP) is a unique protein that consists of both the voltage-sensor domain and phosphoinositide domain. In contrast with intensive studies on its molecular mechanisms, physiological role has not been clear. Here, we report VSP plays critical roles in mouse sperm motility. We found generates polarized distribution PtdIns(4,5)P 2 flagellum, which for regulation ion channel activity calcium influx function. This provides mode by biased .
Phosphoinositide 5′-phosphatases have been implicated in the regulation of phagocytosis. However, their precise roles phagocytic process are poorly understood. We prepared RAW264.7 macrophages deficient Inpp5e (shInpp5e) to clarify role this lipid phosphatase. In shInpp5e cells, uptake solid particles was increased and rate phagosome acidification accelerated. As expected, levels PtdIns(3,4,5)P3 PtdIns(3,4)P2 were decreased respectively, on forming cups these cells. Unexpectedly, most...
Phagocytosis is a highly conserved process whereby phagocytic cells engulf pathogens and apoptotic bodies. The present study focused on the role of inositol polyphosphate-4-phosphatase type I (Inpp4a) in phagocytosis. Raw264.7 that express shRNA against Inpp4a (shInpp4a cells) showed significantly increased activity. introduction shRNA-resistant human abolished this increase. Macrophages from knockout mice similar increases was recruited to phagosome membrane by mechanism other than direct...
ABSTRACT TMEM55a (also known as PIP4P2) is an enzyme that dephosphorylates the phosphatidylinositol (PtdIns) PtdIns(4,5)P2 to form PtdIns(5)P in vitro. However, vivo conversion of polyphosphoinositide into by phosphatase has not yet been demonstrated, and role remains poorly understood. Here, we found mouse macrophages (Raw264.7) deficient showed increased engulfment large particles without affecting phagocytosis Escherichia coli. Transfection a bacterial with similar substrate specificity...
Abstract Male penis is required to become erect during copulation. In the upper (dorsal) part of penis, erectile tissue termed corpus cavernosum (CC) plays fundamental roles for erection by regulating inner blood flow. When flows into CC, microvascular complex sinusoidal space reported expand erection. A novel in vitro explant system analyze dynamic responses contraction/relaxation established. The current data show regulatory processes induced phenylephrine (PE) and nitric oxide (NO) donor...
The relative abundance of phosphoinositide (PI) species on the phagosome membrane fluctuates over course phagocytosis. PtdIns(3,4,5)P3 and PtdIns(3,4)P2 rapidly increase in forming phagocytic cup, following which they disappear after sealing cup. In present study, we monitored clearance these PI using enhanced green fluorescent protein-fused pleckstrin homology domain Akt, a fluorescence probe that binds both Raw 264.7 macrophages. PIs was much faster when phagocytosed particles were coated...
Lysophosphatidylinositol-acyltransferase-1 (LPIAT1) specifically catalyzes the transfer of arachidonoyl-CoA to lysophosphoinositides. LPIAT-/- mice have been shown severe defects in brain and liver; however, exact molecular mechanisms behind these conditions are not well understood. As immune cells implicated liver inflammation based on disfunction LPIAT1, we generated Raw264.7 macrophages deficient using shRNA CRISPR/Cas9. The amount C38:4 species phosphoinositides, especially PtdInsP2 ,...
Macrophages endocytose modified low-density lipoproteins (LDL) vigorously via scavenger receptor A (SR-A) to become foam cells. In the present study, we found that Sac1, a member of Sac family phosphoinositide phosphatases, increases protein level SR-A and upregulates cell formation. Mouse macrophages (RAW264.7) were transfected with short hairpin RNAs (shRNAs) against Sac1. Sac1 knockdown decreased surface levels impaired acetylated LDL-induced Transfection Sac1-knockdown cells...
Abstract Purpose Penile research is expected to reveal new targets for treatment and prevention of the complex mechanisms its disorder including erectile dysfunction (ED). Thus, analyses molecular processes penile ED continuous erection as priapism are essential issues reproductive medicine. Methods By performing mouse N‐ethyl‐N‐nitrosourea mutagenesis exome sequencing, we established a novel line displaying protruded genitalia phenotype (PGP; priapism‐like phenotype) identified Pitpna gene...
Phosphatidylinositol 3-kinase (PI3K)/Akt signaling has been implicated in the anti-inflammatory response a mouse model of endotoxemia and sepsis. The present study focused on role inositol polyphosphate-4-phosphatase type I (Inpp4a), which dephosphorylates PtdIns(3,4)P2 to PtdIns(3)P, bacterial infections. We prepared myeloid cell-specific Inpp4a-conditional knockout mice. Macrophages from these mice showed increased Akt phosphorylation reduced production inflammatory cytokines LPS or...
Voltage-sensing phosphatase (VSP) exhibits voltage-dependent activity toward phosphoinositides. VSP generates a specialized phosphoinositide environment in mammalian sperm flagellum. However, the voltage-sensing mechanism of spermatozoa is not yet characterized. Here, we found that activated during maturation, indicating electric signals immature are essential. Using heterologous expression system, show property mouse (mVSP). The threshold mVSP approximately −30 mV, which sensitive enough to...
Abstract Sac1 is a conserved phosphoinositide phosphatase, whose loss-of-function compromises cell and organism viability. Here, we employed acute auxin-inducible degradation to identify its immediate downstream effectors in human cells. Most of was degraded ∼1 h, paralleled by increased PI(4)P decreased cholesterol the trans-Golgi network (TGN) during following hour, superseded Golgi fragmentation, impaired glycosylation, selective TGN proteins ∼4 h. The disintegration resulted from...
Background: Lipid metabolism plays an essential role in regulating stem and cancer cell function. The enzyme ELOVL6 converts C16 saturated monounsaturated fatty acids (FAs) to C18 species, the most important step for de novo synthesis of endogenous long chain FAs. Variations carbon length or degree desaturation FA greatly contribute lipid diversity. However, whether diversity significantly regulates hematopoietic biology remains unknown. Aims: To clarify how changes composition by Elovl6...