A5029659594- Nuclear Structure and Function
- RNA Research and Splicing
- Genomics and Chromatin Dynamics
- Microtubule and mitosis dynamics
- RNA modifications and cancer
- Lipid Membrane Structure and Behavior
- Cancer-related Molecular Pathways
- SARS-CoV-2 and COVID-19 Research
- Force Microscopy Techniques and Applications
- Reproductive Biology and Fertility
- Cell Adhesion Molecules Research
- Virus-based gene therapy research
- Extracellular vesicles in disease
- Protein Degradation and Inhibitors
- HIV Research and Treatment
- Connexins and lens biology
- Photoreceptor and optogenetics research
- Micro and Nano Robotics
- Glycosylation and Glycoproteins Research
- Nanopore and Nanochannel Transport Studies
- Wnt/β-catenin signaling in development and cancer
- Influenza Virus Research Studies
- Cancer-related gene regulation
- Animal Virus Infections Studies
- Protease and Inhibitor Mechanisms
Life Science Institute
2017-2025
Kanazawa University
2016-2025
Bionomics (Australia)
2017-2025
Frontier Science Foundation
2021
California Animal Hospital
2015
Natural (Czechia)
2013-2015
Institute of Engineering Science
2013
Shanghai Institute for Science of Science
2013
Howard Hughes Medical Institute
2002-2009
Rockefeller University
2006-2009
Independent studies indicate that expression of sialylated fucosylated mucins by human carcinomas portends a poor prognosis because enhanced metastatic spread tumor cells, carcinoma metastasis in mice is facilitated formation cell complexes with blood platelets, and can be attenuated background P-selectin deficiency or treatment heparin. The effects heparin are not primarily due to its anticoagulant action. Other explanations have been suggested but proven. Here, we bring together all these...
P-selectin facilitates human carcinoma metastasis in immunodeficient mice by mediating early interactions of platelets with bloodborne tumor cells via their cell surface mucins, and this process can be blocked heparin [Borsig, L., Wong, R., Feramisco, J., Nadeau, D. Varki, N. M. & A. (2001) Proc. Natl. Acad. Sci. USA 98, 3352–3357]. Here we show similar findings a murine adenocarcinoma syngeneic immunocompetent but involving different ligand, possibly sulfated glycolipid. Thus,...
ZNF750 controls epithelial homeostasis by regulating epidermal-differentiation genes, a role underscored its pathogenic mutations in esophageal squamous cell cancers (SCCs). However, the precise of SCC biology remains unclear. In this study, we report that is exclusively deleted, mutated and underexpressed human SCCs, low expression associated with poor survival. Restoration wildtype, but not mutant protein uniquely inhibited malignant phenotypes cells both vitro vivo. Notably, promoted long...
Abstract Protamines (PRMs) play a crucial role in sperm chromatin condensation, replacing histones to form nucleo–PRM structures, specifically PRM–DNA complexes. Despite their importance reproduction, the detailed mechanisms underlying PRM-mediated DNA condensation have remained elusive. In this study, we employed high-speed atomic force microscopy (HS-AFM) directly visualize real-time binding dynamics of PRM under physiological conditions. Our HS-AFM observations reveal that insertion...
Small extracellular vesicles (sEVs), which carry lipids, proteins and RNAs from their parent cells, serve as biomarkers for specific cell types biological states. These vesicles, including exosomes microvesicles, facilitate intercellular communication by transferring cellular components between cells. Current methods, such ultracentrifugation Tim-4 affinity method, yield high-purity sEVs. However, despite small size, purified sEVs remain heterogeneous due to varied intracellular origins. In...
The kinesin superfamily proteins (KIFs) play essential roles in receptor transportation along the microtubules. KIF17 transports N -methyl- d -aspartate NR2B subunit vitro , but its role vivo is unknown. To clarify this role, we generated transgenic mice overexpressing tagged with GFP. exhibited enhanced learning and memory a series of behavioral tasks, up-regulated expression potential involvement transcriptional factor, cAMP-dependent response element-binding protein, increased...
Key steps in the export of mRNA from nucleus to cytoplasm are transport through nuclear pore complex (NPC) and subsequent remodeling messenger RNA-protein (mRNP) complexes that occurs at cytoplasmic side NPC. Crucial for these events is recruitment DEAD-box helicase Ddx19 filaments NPC mediated by nucleoporin Nup214. Here, we present crystal structure Nup214 N-terminal domain with its ADP-bound state 2.5 A resolution. Strikingly, interaction surfaces not only evolutionarily conserved but...
Abstract SARS‐CoV‐2 spike protein (S) binds to human angiotensin‐converting enzyme 2 (hACE2), allowing virus dock on cell membrane follow by viral entry. Here, we use high‐speed atomic force microscopy (HS‐AFM) for real‐time visualization of S, and its interaction with hACE2 small extracellular vesicles (sEVs). Results show conformational heterogeneity flexibility S stalk receptor‐binding domain (RBD), pH/temperature‐induced change S. in an S‐ACE2 complex appears as all‐RBD up conformation....
In eukaryotic cells, the faithful segregation of daughter chromosomes during cell division depends on formation a microtubule (MT)-based bipolar spindle apparatus. The Nuclear Mitotic Apparatus protein (NuMA) is recruited from interphase nuclei to MTs mitosis. carboxy terminal domain NuMA binds MTs, allowing dimer function as "divalent" crosslinker that bundles MTs. messenger RNA export factor, Rae1, also Lowering Rae1 or increasing levels in cells results abnormalities. We have identified...
Gain or loss of whole chromosomes is often observed in cancer cells and thought to be due aberrant chromosome segregation during mitosis. Proper depends on a faithful interaction between spindle microtubules kinetochores. Several components the nuclear pore complex/nucleoporins play critical roles orchestrating rapid remodeling events that occur Our recent studies revealed nucleoporin, Rae1, plays maintaining bipolarity. Here, we show association another termed Tpr (translocated promoter...
Accurate mitotic chromosome segregation depends on the formation of a microtubule-based bipolar spindle apparatus. We report that cohesin subunit structural maintenance chromosomes 1 (SMC1) is recruited to microtubule-bound RNA export factor (Rae1) at pole. locate Rae1-binding site 21-residue-long region, SMC1(947-967) and provide several lines evidence phosphorylation Ser(957) Ser(966) SMC1 stimulates binding Rae1. Imbalances in these assembly pathways caused multipolar spindles. Our data...
Centrosomes are comprised of 2 orthogonally arranged centrioles surrounded by the pericentriolar material (PCM), which serves as main microtubule organizing center animal cell. More importantly, centrosomes also control spindle polarity and orientation during mitosis. Recently, we other investigators discovered that several nucleoporins play critical roles cell division. Here, show nucleoporin Nup62 plays a novel role in centrosome integrity. Knockdown induced mitotic arrest G2/M phases...
Nuclear pore complexes (NPCs) are the sole turnstile implanted in nuclear envelope (NE), acting as a central nanoregulator of transport between cytosol and nucleus. NPCs consist ∼30 proteins, termed nucleoporins. About one-third nucleoporins harbor natively unstructured, intrinsically disordered phenylalanine-glycine strings (FG-Nups), which engage selectivity. Because barriers insert deeply NPC, they nearly inaccessible. Several vitro barrier models have been proposed; however, dynamic...
Nuclear pore complexes (NPCs) on the nuclear membrane surface have a crucial function in controlling movement of small molecules and macromolecules between cell nucleus cytoplasm through their intricate core channel resembling spiderweb with several layers. Currently, there are few methods available to accurately measure dynamics pores membranes at nanoscale. The limitation traditional optical imaging is due diffraction, which prevents achieving required resolution for observing diverse...
The nuclear pore complex (NPC) consists of a conserved set ~30 different proteins, termed nucleoporins and serves as gateway for the exchange materials between cytoplasm nucleus. Tpr (translocated promoter region) is component NPC that presumably localizes at intranuclear filaments. Here, we show knockdown caused severe reduction in number pores. Furthermore, our electron microscopy studies indicated significant inner In addition, siRNA treatment impaired cell growth proliferation compared...
Chromosomal missegregation is a common feature of many human tumors. Recent studies have indicated link between nucleoporin RanBP2/Nup358 and chromosomal segregation during mitosis; however, the molecular details yet to be fully established. Observed through live cell imaging flow cytometry, here we show that RNA interference-mediated knockdown RanBP2 induced G2/M phase arrest, metaphase catastrophe mitotic death. Furthermore, down-modulation disrupted importin/karyopherin β1 as well...
Children with ependymoma have high mortality rates because is resistant to conventional therapy. Genomic and transcriptomic studies identified potential targets as significantly altered genes in patients. Although several candidate oncogenes were recently reported, the detailed mechanisms for roles of these progression remain unclear. Here, we report an oncogenic role nucleoporin TPR (translocated promoter region, nuclear basket protein) regulating HSF1 (heat shock transcription factor 1)...
Nuclear pore complex (NPC) is a gating nanomachine with central selective barrier composed mainly of Nups, which contain intrinsically disordered (non-structured) regions (IDRs) phenylalanine-glycine (FG) motifs (FG-NUPs). The NPC FG network dynamics poorly understood, as FG-NUPs liquid-liquid phase separation (LLPS) have evaded structural characterization. Moreover, the working mechanism single FG-NUP-biofilaments residing at lumen unknown. In general, flexible biofilaments are expected to...
Nuclear pore complexes (NPC) regulate molecular traffics on nuclear envelope, which plays crucial roles during cell fate specification and diseases. The viral accessory protein NSP9 of SARS-CoV-2 is reported to interact with nucleoporin 62 (NUP62), a structural component the NPC, but its biological impact host remain obscure. Here, we established new line models ectopic expression determined subcellular destination functions NSP9. Confocal imaging identified be largely localized in close...
Small extracellular vesicles (sEVs) play a crucial role in local and distant cell communication. The intrinsic properties of sEVs make them compatible biomaterials for drug delivery, vaccines, theranostic nanoparticles. Although sEV proteomics have been robustly studied, direct instantaneous assessment structure dynamics remains difficult. Here, we use the high-speed atomic force microscopy (HS-AFM) to evaluate nanotopological changes with respect different physicochemical stresses including...
Anti-spike neutralizing antibodies (S NAbs) have been developed for prevention and treatment against COVID-19. The nanoscopic characterization of the dynamic interaction between spike proteins S NAbs remains difficult. By using high-speed atomic force microscopy (HS-AFM), we elucidate molecular property an NAb its with proteins. appeared as monomers a Y conformation at low density formed hexameric oligomers high density. NAb–spike protein RBD induces neither opening nor S1 subunit shedding....