Publications by authors named "Imamoto N"

Nucleocytoplasmic transport is a basic cellular reaction that plays an important role in regulating cell physiology in eukaryotic cells. Here we show that the identification of one nucleocytoplasmic transport pathway led to the notification of intracellular reaction that has not been acknowledged. Hikeshi was originally identified as a nuclear import carrier of heat stress-induced nuclear import of molecular chaperone Hsp70.

View Article and Find Full Text PDF

Nuclear transport is the basis for the biological reaction of eukaryotic cells, as it is essential to coordinate nuclear and cytoplasmic events separated by nuclear envelope. Although we currently understand the basic molecular mechanisms of nuclear transport in detail, many unexplored areas remain. For example, it is believed that the regulations and biological functions of the nuclear transport receptors (NTRs) highlights the significance of the transport pathways in physiological contexts.

View Article and Find Full Text PDF
Article Synopsis
  • Accurate mitotic cell division requires the assembly of replicated chromatin into chromosomes, with proteins like condensin playing crucial roles in this process.
  • Researchers used advanced techniques to study how nucleosomes behave during mitosis in living human cells, discovering that their motion becomes more constrained as chromosomes form.
  • Condensins not only help organize the chromosomes by acting as molecular crosslinkers but also interact with nucleosomes via histone tails, leading to further compaction of entire chromosomes.
View Article and Find Full Text PDF

Heat stress strongly triggers the nuclear localization of the molecular chaperone HSP70. Hikeshi functions as a unique nuclear import carrier of HSP70. However, how the nuclear import of HSP70 is activated in response to heat stress remains unclear.

View Article and Find Full Text PDF

In metazoans, the nuclear envelope (NE) disassembles during the prophase and reassembles around segregated chromatids during the telophase. The process of NE formation has been extensively studied using live-cell imaging. At the early step of NE reassembly in human cells, specific pattern-like localization of inner nuclear membrane (INM) proteins, connected to the nuclear pore complex (NPC), was observed in the so-called "core" region and "noncore" region on telophase chromosomes, which corresponded to the "pore-free" region and the "pore-rich" region, respectively, in the early G1 interphase nucleus.

View Article and Find Full Text PDF

Hikeshi mediates the nuclear import of the molecular chaperone HSP70 under heat-shock (acute heat stress) conditions, which is crucial for recovery from cellular damage. The cytoplasmic function of HSP70 is well studied, but its nuclear roles, particularly under nonstressed conditions, remain obscure. Here, we show that Hikeshi regulates the nucleocytoplasmic distribution of HSP70 not only under heat-shock conditions but also under nonstressed conditions.

View Article and Find Full Text PDF

Saccular limited dorsal myeloschisis (LDM) is characterized by a fibroneural stalk linking the saccular skin lesion to the underlying spinal cord. Since untethering surgery during the early postnatal period is often indicated to prevent sac rupture, saccular LDM should be distinguished from myelomeningocele (MMC) during the perinatal period. We treated two patients with the spinal cord deviation from the spinal canal to the sac, which mimicked a prolapse of the neural placode into the MMC sac.

View Article and Find Full Text PDF

To understand various intranuclear functions, it is important to know when, what, and how proteins enter the nucleus. Although many methods and commercial kits for nuclear fractionation have been developed, there are still no methods for obtaining a complete nuclear proteome. Soluble nuclear proteins are often lost during fractionation.

View Article and Find Full Text PDF

DNA molecules are atomic-scale information storage molecules that promote reliable information transfer via fault-free repetitions of replications and transcriptions. Remarkable accuracy of compacting a few-meters-long DNA into a micrometer-scale object, and the reverse, makes the chromosome one of the most intriguing structures from both physical and biological viewpoints. However, its three-dimensional (3D) structure remains elusive with challenges in observing native structures of specimens at tens-of-nanometers resolution.

View Article and Find Full Text PDF

Importin-(Imp)β family nucleocytoplasmic transport receptors (NTRs) are supposed to bind to their cargoes through interaction between a confined interface on an NTR and a nuclear localization or export signal (NLS/NES) on a cargo. Although consensus NLS/NES sequence motifs have been defined for cargoes of some NTRs, many experimentally identified cargoes of those NTRs lack those motifs, and consensus NLSs/NESs have been reported for only a few NTRs. Crystal structures of NTR-cargo complexes have exemplified 3D structure-dependent binding of cargoes lacking a consensus NLS/NES to different sites on an NTR.

View Article and Find Full Text PDF

Mouse telomerase and the DNA polymerase alpha-primase complex elongate the leading and lagging strands of telomeres, respectively. To elucidate the molecular mechanism of lagging strand synthesis, we investigated the interaction between DNA polymerase alpha and two paralogs of the mouse POT1 telomere-binding protein (POT1a and POT1b). Yeast two-hybrid analysis and a glutathione S-transferase pull-down assay indicated that the C-terminal region of POT1a/b binds to the intrinsically disordered N-terminal region of p180, the catalytic subunit of mouse DNA polymerase alpha.

View Article and Find Full Text PDF

A 29-year-old man after the Fontan operation had a catastrophic intracranial hemorrhage associated with eosinophilic granulomatous polyangiitis. Despite combination therapy with cyclophosphamide and methylprednisolone, he was dead at 6 months after the onset. The clinical course was worse owing to underlying coagulopathy and endothelial dysfunction associated with congenital heart disease.

View Article and Find Full Text PDF

IER5 gene encodes an activator of HSF1 and is a p53 target gene. The IER5 protein forms a ternary complex with HSF1 and PP2A, and promotes PP2A-dependent dephosphorylation of HSF1 at a number of serine and threonine residues. This hypo-phosphorylated form of HSF1 is transcriptionally active and has been suggested to be responsible for the HSF1 activation observed in cancers.

View Article and Find Full Text PDF
Article Synopsis
  • Cells have a specific temperature range for optimal growth, and when temperatures deviate, they activate protective mechanisms, but the exact temperature points for different cellular responses remain unclear.
  • A new temperature shift assay revealed that different nuclear transport pathways respond variably to increased temperatures, with the chaperone HSP70s translocating at lower temperatures than other transport mechanisms.
  • The study found that the import of proteins via importin (Imp) α/β is inhibited at lower temperatures due to dysfunction of Imp α1, indicating that various transport systems react independently to heat stress.
View Article and Find Full Text PDF

Background: A retained medullary cord (RMC) is a rare closed spinal dysraphism with a robust elongated neural structure continuous from the conus and extending to the dural cul-de-sac. Four cases of RMC extending down to the base of an associated subcutaneous meningocele at the sacral level have been reported.

Clinical Presentation: We report an additional case of RMC, in whom serial MRI examination revealed an enlargement of the meningocele associated with RMC over a 3-month period between 8 and 11 months of age, when he began to stand.

View Article and Find Full Text PDF

The Y-box proteins are multifunctional nucleic acid-binding proteins involved in various aspects of gene regulation. The founding member of the Y-box protein family, YB-1, functions as a transcription factor as well as a principal component of messenger ribonucleoprotein particles (mRNPs) in somatic cells. The nuclear level of YB-1 is well correlated with poor prognosis in many human cancers.

View Article and Find Full Text PDF

The prime feature of eukaryotic cells is the separation of the intracellular space into two compartments, the nucleus and the cytoplasm. Active nuclear transport is crucial for the maintenance of this separation. In this report, we focus on a nuclear transport receptor named Hikeshi, which mediates the heat stress-induced nuclear import of 70-kDa heat shock proteins (Hsp70s), and discuss how the same protein can function differently depending on the cellular compartment in which it is localized.

View Article and Find Full Text PDF

Although condensins play essential roles in mitotic chromosome assembly, Ki-67 (also known as MKI67), a protein localizing to the periphery of mitotic chromosomes, had also been shown to make a contribution to the process. To examine their respective roles, we generated a set of HCT116-based cell lines expressing Ki-67 and/or condensin subunits that were fused with an auxin-inducible degron for their conditional degradation. Both the localization and the dynamic behavior of Ki-67 on mitotic chromosomes were not largely affected upon depletion of condensin subunits, and vice versa.

View Article and Find Full Text PDF

β-catenin acts as a key mediator of Wnt signaling by migrating into the nucleus. In this issue of Developmental Cell, Griffin et al. (2018) propose that facilitated nuclear import of β-catenin is actively regulated by the nuclear small GTPase Rap through its guanine nucleotide exchange factor, RAPGEF5.

View Article and Find Full Text PDF

Nuclear pore complexes (NPCs) maintain cellular homeostasis by mediating nucleocytoplasmic transport. Although cyclin-dependent kinases (CDKs) regulate NPC assembly in interphase, the location of NPC assembly on the nuclear envelope is not clear. CDKs also regulate the disappearance of pore-free islands, which are nuclear envelope subdomains; this subdomain gradually disappears with increase in homogeneity of the NPC in response to CDK activity.

View Article and Find Full Text PDF

Hikeshi mediates the heat stress-induced nuclear import of heat-shock protein 70 (HSP70s: HSP70/HSC70). Dysfunction of Hikeshi causes some serious effects in humans; however, the cellular function of Hikeshi is largely unknown. Here, we investigated the effects of Hikeshi depletion on the survival of human cells after proteotoxic stress and found opposite effects in HeLa and hTERT-RPE1 (RPE) cells; depletion of Hikeshi reduced the survival of HeLa cells, but increased the survival of RPE cells in response to proteotoxic stress.

View Article and Find Full Text PDF

The protein mini-chromosome maintenance 10 (Mcm10) was originally identified as an essential yeast protein in the maintenance of mini-chromosome plasmids. Subsequently, Mcm10 has been shown to be required for both initiation and elongation during chromosomal DNA replication. However, it is not fully understood how the multiple functions of Mcm10 are coordinated or how Mcm10 interacts with other factors at replication forks.

View Article and Find Full Text PDF

Vast numbers of proteins are transported into and out of the nuclei by approximately 20 species of importin-β family nucleocytoplasmic transport receptors. However, the significance of the multiple parallel transport pathways that the receptors constitute is poorly understood because only limited numbers of cargo proteins have been reported. Here, we identified cargo proteins specific to the 12 species of human import receptors with a high-throughput method that employs stable isotope labeling with amino acids in cell culture, an in vitro reconstituted transport system, and quantitative mass spectrometry.

View Article and Find Full Text PDF

Lamin B receptor (LBR), an inner nuclear membrane (INM) protein, contributes to the functional integrity of the nucleus by tethering heterochromatin to the nuclear envelope. We have previously reported that the depletion of embryonic large molecule derived from yolk sac (ELYS; also known as AHCTF1), a component of the nuclear pore complex, from cells perturbs the localization of LBR to the INM, but little is known about the underlying molecular mechanism. In this study, we found that the depletion of ELYS promoted LBR phosphorylation at the residues known to be phosphorylated by cyclin-dependent kinase (CDK) and serine/arginine protein kinases 1 and 2 (SRPK1 and SRPK2, respectively).

View Article and Find Full Text PDF