A5066468783- Advanced Electron Microscopy Techniques and Applications
- Neuroscience and Neuropharmacology Research
- RNA and protein synthesis mechanisms
- Neural dynamics and brain function
- Sleep and Wakefulness Research
- Microtubule and mitosis dynamics
- Sperm and Testicular Function
- RNA Research and Splicing
- Memory and Neural Mechanisms
- Force Microscopy Techniques and Applications
- Photoreceptor and optogenetics research
- Plant Molecular Biology Research
- RNA modifications and cancer
- Genomics and Chromatin Dynamics
- Functional Brain Connectivity Studies
- Plant nutrient uptake and metabolism
- Molecular Biology Techniques and Applications
- RNA regulation and disease
- Pancreatic function and diabetes
- CRISPR and Genetic Engineering
- Chromosomal and Genetic Variations
- Diabetes Treatment and Management
- Genetics and Neurodevelopmental Disorders
- Renal and related cancers
- Advanced Memory and Neural Computing
Howard Hughes Medical Institute
2021-2024
Janelia Research Campus
2021-2024
Helix (United States)
2024
RIKEN Center for Brain Science
2018-2020
Osaka City General Hospital
2011
The flagella of mammalian sperm display non-planar, asymmetric beating, in contrast to the planar, symmetric beating from sea urchin and unicellular organisms. molecular basis this difference is unclear. Here, we perform situ cryo-electron tomography mouse human sperm, providing highest-resolution structural information date. Our subtomogram averages reveal sperm-specific protein complexes within microtubules, radial spokes nexin-dynein regulatory complexes. locations structures these...
To understand the molecular mechanisms of cellular pathways, contemporary workflows typically require multiple techniques to identify proteins, track their localization, and determine structures in vitro. Here, we combined cryoelectron tomography (cryo-ET) AlphaFold2 modeling address these questions how mammalian sperm are built situ. Our cryo-ET subtomogram averaging provided 6.0-Å reconstructions axonemal microtubule structures. The well-resolved tertiary allowed us unbiasedly match...
Yorifuji T, Fujimaru R, Hosokawa Y, Tamagawa N, Shiozaki M, Aizu K, Jinno Maruo Nagasaka H, Tajima Kobayashi Urakami T. Comprehensive molecular analysis of Japanese patients with pediatric-onset MODY-type diabetes mellitus. Background: In Asians, mutations in the known maturity-onset young (MODY) genes have been identified only <15% patients. These results were obtained mostly through studies on adult Objective: To investigate basis diabetes. Subjects: Eighty Methods: Mitochondrial 3243A>G...
Significance RDR2 is critical for siRNA-directed DNA methylation in Arabidopsis , functioning physical association with DNA-dependent Pol IV to synthesize the second strands of double-stranded siRNA precursors. Base-pairing between template strand transcribed by and nontemplate needed induce arrest IV/RDR2 transcriptional coupling, but how this occurs unknown. We report structure experimental evidence engages its RNA templates initiates transcription. ends RNAs displaced from RNA/DNA...
Chemical synapses are the major sites of communication between neurons in nervous system and mediate either excitatory or inhibitory signaling. At synapses, glutamate is primary neurotransmitter upon release from presynaptic vesicles, detected by postsynaptic receptors, which include ionotropic AMPA NMDA receptors. Here, we have developed methods to identify glutamatergic brain tissue slices, label receptors with small gold nanoparticles (AuNPs), prepare lamella for cryo-electron tomography...
Biomolecular condensates, compartments that concentrate molecules without surrounding membranes, are integral to numerous cellular processes. The structure and interaction networks of within condensates remain poorly understood. Using cryo-electron tomography molecular dynamics simulations we elucidated the phase separated chromatin across scales, from individual amino acids network architecture. We found internucleosomal DNA linker length controls nucleosome arrangement histone tail...
RNA-guided systems, such as CRISPR-Cas, combine programmable substrate recognition with enzymatic function, a combination that has been used advantageously to develop powerful molecular technologies
Phase separation is an important mechanism to generate certain biomolecular condensates and organize the cell interior. Condensate formation function remain incompletely understood due difficulties in visualizing condensate interior at high resolution. Here we analyzed structure of biochemically reconstituted chromatin through cryo-electron tomography. We found that traditional blotting methods sample preparation were inadequate, high-pressure freezing plus focused ion beam milling was...
Summary Chemical synapses are the major sites of communication between neurons in nervous system and mediate either excitatory or inhibitory signaling [1]. At synapses, glutamate is primary neurotransmitter upon release from presynaptic vesicles, detected by postsynaptic receptors, which include ionotropic AMPA NMDA receptors [2, 3]. Here we have developed methods to identify glutamatergic brain tissue slices, label with small gold nanoparticles (AuNPs), prepare lamella for cryo-electron...
Chemical synapses are the major sites of communication between neurons in nervous system and mediate either excitatory or inhibitory signaling [1]. At synapses, glutamate is primary neurotransmitter upon release from presynaptic vesicles, detected by postsynaptic receptors, which include ionotropic AMPA NMDA receptors [2, 3]. Here we have developed methods to identify glutamatergic brain tissue slices, label with small gold nanoparticles (AuNPs), prepare lamella for cryo-electron tomography...
Chemical synapses are the major sites of communication between neurons in nervous system and mediate either excitatory or inhibitory signaling. At synapses, glutamate is primary neurotransmitter upon release from presynaptic vesicles, detected by postsynaptic receptors, which include ionotropic AMPA NMDA receptors. Here, we have developed methods to identify glutamatergic brain tissue slices, label receptors with small gold nanoparticles (AuNPs), prepare lamella for cryo-electron tomography...
Chemical synapses are the major sites of communication between neurons in nervous system and mediate either excitatory or inhibitory signaling [1]. At synapses, glutamate is primary neurotransmitter upon release from presynaptic vesicles, detected by postsynaptic receptors, which include ionotropic AMPA NMDA receptors [2, 3]. Here we have developed methods to identify glutamatergic brain tissue slices, label with small gold nanoparticles (AuNPs), prepare lamella for cryo-electron tomography...
Abstract During sleep and awake rest, the neocortex generates large-scale slow-wave activity. Here we report that claustrum, a poorly understood subcortical neural structure, coordinates neocortical generation. We established transgenic mouse line allowing genetic electrophysiological interrogation of subpopulation claustral glutamatergic neurons. These excitatory neurons received inputs from in large network. Optogenetic activation vitro induced post-synaptic responses most neurons, but...
Abstract Understanding molecular mechanisms of cellular pathways requires knowledge the identities participating proteins, their localization and 3D structures. Contemporary workflows typically require multiple techniques to identify target track using fluorescence microscopy, followed by in vitro structure determination. To mammal-specific sperm proteins understand functions, we developed a visual proteomics workflow directly address these challenges. Our situ cryo-electron tomography...
Abstract The flagella of mammalian sperm display non-planar, asymmetric beating, in contrast to the planar, symmetric beating from sea urchin and unicellular organisms. molecular basis this difference is unclear. Here, we perform situ cryo-electron tomography mouse human axonemes, providing highest resolution structural information date. Our subtomogram averages reveal sperm- specific protein complexes within outer microtubule doublets, radial spokes nexin-dynein regulatory complexes....
Ionotropic glutamate receptors (iGluRs) at postsynaptic terminals mediate the majority of fast excitatory neurotransmission in response to release from presynaptic terminal. Obtaining structural information on molecular organization iGluRs their native environment, along with other signaling and scaffolding proteins density (PSD), associated terminal, would enhance understanding basis for synaptic transmission normal disease states. Cryo-electron tomography (ET) studies synaptosomes is one...
Abstract RNA-dependent RNA polymerases play essential roles in RNA-mediated gene silencing eukaryotes. In Arabidopsis , RNA-DEPENDENT POLYMERASE 2 (RDR2) physically interacts with DNA-dependent NUCLEAR IV (Pol IV) and their activities are tightly coupled, Pol transcriptional arrest or termination, involving the nontemplate DNA strand, somehow enabling RDR2 to engage transcripts generate double-stranded RNAs. The dsRNAs then released from IV-RDR2 complex diced into siRNAs that guide...
Ionotropic glutamate receptors (iGluRs) at postsynaptic terminals mediate the majority of fast excitatory neurotransmission in response to release from presynaptic terminal. Obtaining structural information on molecular organization iGluRs their native environment, along with other signaling and scaffolding proteins density (PSD), associated terminal, would enhance understanding basis for synaptic transmission normal disease states. Cryo-electron tomography (ET) studies synaptosomes is one...