Transmembrane proteins of tight junctions

AbstractTight junctions contribute to the paracellular barrier, the fence dividing plasma membranes, and signal transduction, acting as a multifunctional complex in vertebrate epithelial and endothelial cells. The identification and characterization of the transmembrane proteins of tight junctions, claudins, junctional adhesion molecules (JAMs), occludin and tricellulin, have led to insights into the molecular nature of tight junctions. We provide an overview of recent progress in studies on these proteins and highlight their roles and regulation, as well as their functional significance in human diseases

Experimental effect of retinoic acids on apoptosis during the development of diabetic retinopathy

Nami Nishikiori1,2, Makoto Osanai2, Hideki Chiba2, Takashi Kojima2, Shuichiro Inatomi1,2, Hiroshi Ohguro1, Norimasa Sawada2Departments of 1Ophthalmology and 2Pathology, Sapporo Medical University School of MedicinePurpose: This study was conducted to investigate whether retinoic acids (RAs) had any effect on apoptosis during the development of diabetic retinopathy.Methods: To investigate whether RAs had any effect on apoptosis during the development of diabetic retinopathy, we housed 32 C57BL/6 male mice and induced diabetes in 24 by intra peritoneal injections of streptozotocin (STZ; Sigma, St Louis, MO) and treated 16 of the diabetic mice with the RAs, all-trans-retinoic acid (ATRA) (seven mice) and 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carboxamido] benzoic acid (Am580) (nine mice). The other eight mice were used as diabetic controls. We then measured apoptosis in the retina by TdT-dUTP terminal nick-end labeling assay.Results: RAs inhibited the apoptosis of retinal cells in diabetic retinopathy. Many apoptotic cells were observed in retinas of the eight diabetic control mice (mean value and SD: 37.8 ± 6.9), whereas when diabetic mice were treated with RAs, the number of apoptotic cells significantly decreased (mean value and SD: 9.9 ± 6.4 for the seven ATRA-treated diabetic mice and 9.8 ± 5.9 for the nine Am580-treated diabetic mice) (p < 0.05).Conclusion: Treatment with RAs decreases apoptosis during the development of diabetic retinopathy.Keywords: retinoic acids, apoptosis, diabetic retinopathy, glial cell line-derived neurotrophic facto

The nuclear receptor hepatocyte nuclear factor 4α acts as a morphogen to induce the formation of microvilli

Microvilli are actin-based organelles found on apical plasma membranes that are involved in nutrient uptake and signal transduction. Numerous components, including ezrin/radixin/moesin (ERM) proteins, have been identified that link filamentous actins to transmembrane proteins, but the signals driving microvillus biogenesis are not known. In this study, we show that the conditional and/or ectopic expression of a nuclear receptor, hepatocyte nuclear factor 4α (HNF4α), triggers microvillus morphogenesis. We also demonstrate that HNF4α expression induces ERM-binding phosphoprotein 50 (EBP50) expression and that attenuation of EBP50 using RNA interference inhibits microvillus development. We conclude that HNF4α acts as a morphogen to trigger microvillus formation

Quantitative activation-induced manganese-enhanced MRI reveals severity of Parkinson’s disease in mice

We demonstrate that activation-induced manganese-enhanced magnetic resonance imaging with quantitative determination of the longitudinal relaxation time (qAIM-MRI) reveals the severity of Parkinson’s disease (PD) in mice. We first show that manganese ion-accumulation depends on neuronal activity. A highly active region was then observed by qAIM-MRI in the caudate-putamen in PD-model mice that was significantly correlated to the severity of PD, suggesting its involvement in the expression of PD symptoms

Cav2.3 (α1E) Ca2+ channel participates in the control of sperm function

AbstractTo know the function of the Ca2+ channel containing α12.3 (α1E) subunit (Cav2.3 channel) in spermatozoa, we analyzed Ca2+ transients and sperm motility using a mouse strain lacking Cav2.3 channel. The averaged rising rates of Ca2+ transients induced by α-D-mannose–bovine serum albumin in the head region of Cav2.3−/− sperm were significantly lower than those of Cav2.3+/+ sperm. A computer-assisted sperm motility assay revealed that straight-line velocity and linearity were greater in Cav2.3−/− sperm than those in Cav2.3+/+ sperm. These results suggest that the Cav2.3 channel plays some roles in Ca2+ transients and the control of flagellar movement

Orchestrated ensemble activities constitute a hippocampal memory engram

The brain stores and recalls memories through a set of neurons, termed engram cells. However, it is unclear how these cells are organized to constitute a corresponding memory trace. We established a unique imaging system that combines Ca2+ imaging and engram identification to extract the characteristics of engram activity by visualizing and discriminating between engram and non-engram cells. Here, we show that engram cells detected in the hippocampus display higher repetitive activity than non-engram cells during novel context learning. The total activity pattern of the engram cells during learning is stable across post-learning memory processing. Within a single engram population, we detected several sub-ensembles composed of neurons collectively activated during learning. Some sub-ensembles preferentially reappear during post-learning sleep, and these replayed sub-ensembles are more likely to be reactivated during retrieval. These results indicate that sub-ensembles represent distinct pieces of information, which are then orchestrated to constitute an entire memory

Spatiotemporal Properties of the Action Potential Propagation in the Mouse Visual Cortical Slice Analyzed by Calcium Imaging

The calcium ion (Ca2+) is an important messenger for signal transduction, and the intracellular Ca2+ concentration ([Ca2+]i) changes in response to an excitation of the cell. To reveal the spatiotemporal properties of the propagation of an excitatory signal with action potentials in the primary visual cortical circuit, we conducted a Ca2+ imaging study on slices of the mouse visual cortex. Electrical stimulation of layer 4 evoked [Ca2+]i transients around the stimulus electrode. Subsequently, the high [Ca2+]i region mainly propagated perpendicular to the cortical layer (vertical propagation), with horizontal propagation being restricted. When the excitatory synaptic transmission was blocked, only weak and concentric [Ca2+]i transients were observed. When the action potential was blocked, the [Ca2+]i transients disappeared almost completely. These results suggested that the action potential contributed to the induction of the [Ca2+]i transients, and that excitatory synaptic connections were involved in the propagation of the high [Ca2+]i region in the primary visual cortical circuit. To elucidate the involvement of inhibitory synaptic connections in signal propagation in the primary visual cortex, the GABAA receptor inhibitor bicuculline was applied. In this case, the evoked signal propagated from layer 4 to the entire field of view, and the prolonged [Ca2+]i transients were observed compared with the control condition. Our results suggest that excitatory neurons are widely connected to each other over the entire primary visual cortex with recurrent synapses, and inhibitory neurons play a fundamental role in the organization of functional sub-networks by restricting the propagation of excitation signals

Activated macrophages promote invasion by early colorectal cancer via an IL-1β-SAA1 axis

本研究は，低分化成分に着目して早期大腸がんの分子解析を行った．T1 大腸がんの臨床検体を用いたRNA-seqを行い，低分化成分でのserum amyloid A1（SAA1）の高発現を同定した．大腸がん細胞を用いた機能解析，マクロファージとの共培養実験，臨床検体の免疫染色解析の結果，T1大腸がんの浸潤先進部では，マクロファージとがん細胞がIL-1βとSAA1を介して相互作用することで浸潤を促進すると考えられ，SAA1が早期大腸がんの治療層別化マーカーおよび治療標的となる可能性が示唆された