C-type lectin Mincle-dependent and -independent activation of invariant NKT cells by exposure to Helicobacter pylori α-cholesteryl glucosides.

Helicobacter pylori extracts cholesterol from the host and converts it to its glycosides. We found that cholesteryl 6'-O-acyl α-glucoside (ChAcαG) produced by H. pylori is recognised by both invariant Vα14 NKT (iNKT) cells and a C-type lectin receptor Mincle (Clec4e).

Selective targeting of mRNA and the following protein synthesis of CaMKIIα at the long-term potentiation-induced site.

Late-phase long-term potentiation (L-LTP) in hippocampus, thought to be the cellular basis of long-term memory, requires new protein synthesis. Neural activity enhances local protein synthesis in dendrites, which in turn mediates long-lasting synaptic plasticity. Ca/calmodulin-dependent protein kinase IIα (CaMKIIα) is a locally synthesized protein crucial for this plasticity, as L-LTP is impaired when its local synthesis is eliminated.

Invariant natural killer T cells stimulated with cholesteryl glycosides modulate immune responses in allergy and delayed-type hypersensitivity.

Invariant NKT cells were stimulated with cholesteryl O-acyl α-glycosides in the context of CD1d. The activated NKT cells have potential to sustain the homeostasis in the body exposed to excess in either Th1- or Th2-immunity.

UBL3 modification influences protein sorting to small extracellular vesicles.

Exosomes, a type of small extracellular vesicles (sEVs), derived from multivesicular bodies (MVBs), mediate cell-to-cell communication by transporting proteins, mRNAs, and miRNAs. However, the molecular mechanism by which proteins are sorted to sEVs is not fully understood. Here, we report that ubiquitin-like 3 (UBL3)/membrane-anchored Ub-fold protein (MUB) acts as a posttranslational modification (PTM) factor that regulates protein sorting to sEVs.

Activation of invariant natural killer T cells stimulated with microbial α-mannosyl glycolipids.

Some synthetic and bacterial glycolipids presented by CD1d specifically activate invariant NKT (iNKT) cells bearing an invariant Vα14-Jα18 (mouse) or Vα24-Jα18 (human) TCR. The antigenic glycolipids identified to date consist of two hydrophobic chains and an α-glycoside in which the 2'-OH group is in the cis orientation toward the anomeric group, namely, either an α-galactoside or an α-glucoside. Several microbial α-mannosyl glycolipids, in which the 2'-OH group is in the trans orientation, were herein examined to establish whether they have potential to activate iNKT cells.

Proper cytoskeletal architecture beneath the plasma membrane of red blood cells requires .

Mammalian red blood cells (RBCs) circulate through blood vessels, including capillaries, for tens of days under high mechanical stress. RBCs tolerate this mechanical stress while maintaining their shape because of their elastic membrane skeleton. This membrane skeleton consists of spectrin-actin lattices arranged as quasi-hexagonal units beneath the plasma membrane.

Targeting of ribosomal protein S6 to dendritic spines by in vivo high frequency stimulation to induce long-term potentiation in the dentate gyrus.

Late phase long-term potentiation (L-LTP) in the hippocampus is believed to be the cellular basis of long-term memory. Protein synthesis is required for persistent forms of synaptic plasticity, including L-LTP. Neural activity is thought to enhance local protein synthesis in dendrites, and one of the mechanisms required to induce or maintain the long-lasting synaptic plasticity is protein translation in the dendrites.

Na, K-ATPase α3 is a death target of Alzheimer patient amyloid-β assembly.

Neurodegeneration correlates with Alzheimer's disease (AD) symptoms, but the molecular identities of pathogenic amyloid β-protein (Aβ) oligomers and their targets, leading to neurodegeneration, remain unclear. Amylospheroids (ASPD) are AD patient-derived 10- to 15-nm spherical Aβ oligomers that cause selective degeneration of mature neurons. Here, we show that the ASPD target is neuron-specific Na(+)/K(+)-ATPase α3 subunit (NAKα3).

Mammalian Bcnt/Cfdp1, a potential epigenetic factor characterized by an acidic stretch in the disordered N-terminal and Ser250 phosphorylation in the conserved C-terminal regions.

The BCNT (Bucentaur) superfamily is classified by an uncharacteristic conserved sequence of ∼80 amino acids (aa) at the C-terminus, BCNT-C (the conserved C-terminal region of Bcnt/Cfdp1). Whereas the yeast Swc5 and Drosophila Yeti homologues play crucial roles in chromatin remodelling organization, mammalian Bcnt/Cfdp1 (craniofacial developmental protein 1) remains poorly understood. The protein, which lacks cysteine, is largely disordered and comprises an acidic N-terminal region, a lysine/glutamic acid/proline-rich 40 aa sequence and BCNT-C.

Sirh7/Ldoc1 knockout mice exhibit placental P4 overproduction and delayed parturition.

Sirh7/Ldoc1 [sushi-ichi retrotransposon homolog 7/leucine zipper, downregulated in cancer 1, also called mammalian retrotransposon-derived 7 (Mart7)] is one of the newly acquired genes from LTR retrotransposons in eutherian mammals. Interestingly, Sirh7/Ldoc1 knockout (KO) mice exhibited abnormal placental cell differentiation/maturation, leading to an overproduction of placental progesterone (P4) and placental lactogen 1 (PL1) from trophoblast giant cells (TGCs). The placenta is an organ that is essential for mammalian viviparity and plays a major endocrinological role during pregnancy in addition to providing nutrients and oxygen to the fetus.

Inactivation of TRPM7 kinase activity does not impair its channel function in mice.

Transient receptor potential (TRP) family channels are involved in sensory pathways and respond to various environmental stimuli. Among the members of this family, TRPM7 is a unique fusion of an ion channel and a C-terminus kinase domain that is highly expressed in immune cells. TRPM7 serves as a key molecule governing cellular Mg(2+) homeostasis in mammals since its channel pore is permeable to Mg(2+) ions and can act as a Mg(2+) influx pathway.

Rasa3 controls megakaryocyte Rap1 activation, integrin signaling and differentiation into proplatelet.

Rasa3 is a GTPase activating protein of the GAP1 family which targets Ras and Rap1. Ubiquitous Rasa3 catalytic inactivation in mouse results in early embryonic lethality. Here, we show that Rasa3 catalytic inactivation in mouse hematopoietic cells results in a lethal syndrome characterized by severe defects during megakaryopoiesis, thrombocytopenia and a predisposition to develop preleukemia.

Repression of cyclin D1 expression is necessary for the maintenance of cell cycle exit in adult mammalian cardiomyocytes.

The hearts of neonatal mice and adult zebrafish can regenerate after injury through proliferation of preexisting cardiomyocytes. However, adult mammals are not capable of cardiac regeneration because almost all cardiomyocytes exit their cell cycle. Exactly how the cell cycle exit is maintained and how many adult cardiomyocytes have the potential to reenter the cell cycle are unknown.

Histone H3 lysine 9 methyltransferases, G9a and GLP are essential for cardiac morphogenesis.

Lysine methylation of the histone tail is involved in a variety of biological events. G9a and GLP are known as major H3-K9 methyltransferases and contribute to transcriptional silencing. The functions of these genes in organogenesis remain largely unknown.

Balanced ubiquitination determines cellular responsiveness to extracellular stimuli.

Signal strength evoked by ligand stimulation is crucial for cellular responses such as fate decision, cell survival/death, secretion, and migration. For example, morphogens are secreted signaling molecules that form concentration gradients within tissues and induce distinct cell fates in a signal strength-dependent manner. In addition to extracellular ligand abundance, the sensitivity of signal-receiving cells to ligands also influences signal strength.

Sequential insertion of multiple I-SceI recognition sites at designed loci of the Bacillus subtilis 168 genome.

Bacillus subtilis 168 is the only bacterium-based host serving for the cloning of giant DNA above 1.000 kbp. As rapid verification of the genome structure is crucial during the cloning process, six of 18-base sequence recognized by endonuclease I-SceI were sequentially created in the B.

Functional expression of a two-transmembrane HtrII protein using cell-free synthesis.

An approach of cell-free synthesis is presented for the functional expression of transmembrane proteins without the need of refolding. The transmembrane region of the halobacterial transducer protein, HtrII, was translated with various large soluble tags added ( protein and maltose binding protein). In this system, all fusion HtrII were translated in a soluble fraction, presumably, forming giant micelle-like structures.

Transformation of eEF1Bδ into heat-shock response transcription factor by alternative splicing.

Protein translation factors have crucial roles in a variety of stress responses. Here, we show that eukaryotic elongation factor 1Bδ (eEF1Bδ) changes its structure and function from a translation factor into a heat-shock response transcription factor by alternative splicing. The long isoform of eEF1Bδ (eEF1BδL) is localized in the nucleus and induces heat-shock element (HSE)-containing genes in cooperation with heat-shock transcription factor 1 (HSF1).

Forebrain-specific constitutively active CaMKKα transgenic mice show deficits in hippocampus-dependent long-term memory.

The Ca(2+)/calmodulin (CaM) kinase cascade is activated by Ca(2+) influx through the voltage-dependent Ca(2+) channels and the NMDA receptor. CaM kinase kinase (CaMKK), the most upstream kinase of the CaM kinase cascade, phosphorylates and activates both CaM kinase I (CaMKI) and CaMKIV, resulting in activation of cyclic AMP-responsive element binding protein (CREB)-dependent gene transcription. Using transgenic techniques, we created mutant mice in which a constitutively active form of CaMKK1, the autoinhibitory domain truncated protein, is over-expressed specifically in the forebrain.

Coordinated regulation of differentiation and proliferation of embryonic cardiomyocytes by a jumonji (Jarid2)-cyclin D1 pathway.

In general, cell proliferation and differentiation show an inverse relationship, and are regulated in a coordinated manner during development. Embryonic cardiomyocytes must support embryonic life by functional differentiation such as beating, and proliferate actively to increase the size of the heart. Therefore, progression of both proliferation and differentiation is indispensable.

Two distinct amyloid beta-protein (Abeta) assembly pathways leading to oligomers and fibrils identified by combined fluorescence correlation spectroscopy, morphology, and toxicity analyses.

Nonfibrillar assemblies of amyloid β-protein (Aβ) are considered to play primary roles in Alzheimer disease (AD). Elucidating the assembly pathways of these specific aggregates is essential for understanding disease pathogenesis and developing knowledge-based therapies. However, these assemblies cannot be monitored in vivo, and there has been no reliable in vitro monitoring method at low protein concentration.

Accelerated modification of the zona pellucida is the primary cause of decreased fertilizability of oocytes in the 129 inbred mouse strain.

We investigated whether the small litter size in the 129 inbred mouse strain results from a reduction in oocyte fertilizability. Sensitivity of the zona pellucida to α-chymotrypsin was examined for oocytes collected at 14 h (shortly after ovulation), 17 h, and 20 h after hCG injection. Passage of spermatozoa through the zona pellucida (using an in vitro fertilization (IVF) technique) and the density of cortical granules were examined for oocytes collected at 14 and 17 h after hCG injection.

Identification of genes required for neural-specific glycosylation using functional genomics.

Glycosylation plays crucial regulatory roles in various biological processes such as development, immunity, and neural functions. For example, α1,3-fucosylation, the addition of a fucose moiety abundant in Drosophila neural cells, is essential for neural development, function, and behavior. However, it remains largely unknown how neural-specific α1,3-fucosylation is regulated.

Inhibition of ganglioside synthesis reduces the neuronal survival activity of astrocytes.

Gangliosides are sialic acid-containing sphingolipids that have promoting effects on the survival, growth, and functions of neurons in the central nervous system. Glial cells including astrocytes assist neurons with regard to their proliferation, maintenance, and function. In the present study, we found that astrocytes with ganglioside depletion caused by treatment with d-threo-1-phenyl-1-2-decanoylamino-3-morpholino-1-propanol (d-PDMP) exhibited reduced neuronal survival activity, as evaluated using low-density hippocampal cultures.

Regulation of immunological disorders by invariant Vα19-Jα33 TCR-bearing cells.

We have previously shown that over-expression of the invariant Vα19-Jα33 TCR α transgene (Tg) using a natural TCR α promoter in mice induces the development of NK1.1(+) T cells (Vα19 NKT cells) in lymphoid organs, including the liver and intestine. These cells produce different spectra of immunoregulatory cytokines such as IL-4, IL-10, IL-17, and IFN-γ depending on the duration and intensity of the invariant TCR stimulation.