Using PrPC-knockout cell lines, it has been shown that the inhibition of apoptosis through STI1 is mediated by PrPC-dependent SOD activation. Antioxidant PrPC may contribute to suppression of inflammasome activation. PrPC is functionally involved in copper metabolism, signal transduction, neuroprotection, and cell maturation. Recently several reports have shown that PrPC participates in trans-membrane signaling processes associated with hematopoietic stem cell replication and neuronal differentiation. In another role, PrPC also tends to function as a neurotoxic protein. Aβ oligomer, which is associated with neurodegeneration in Alzheimer’s disease (AD), has also been reported to act as a ligand of PrPC. However, the physiological role of PrPC as an Aβ42-binding protein is not clear. Actually, PrPC is critical in Aβ42-mediated autophagy in neurons. PrPC shows a beneficial role in lipid rafts to promote autophagy. Further search for PrPC-interaction molecules using Prnp−/− mice and various types of Prnp−/− cell lines under various conditions may elucidate other important PrPC important functions.
Nerve injury often causes debilitating chronic pain, referred to as neuropathic pain, which is refractory to currently available analgesics including morphine. Many reports indicate that activated spinal microglia evoke neuropathic pain. The P2X4 receptor (P2X4R), a subtype of ionotropic ATP receptors, is upregulated in spinal microglia after nerve injury by several factors, including CC chemokine receptor CCR2, the extracellular matrix protein fibronectin in the spinal cord, interferon regulatory factor 8 (IRF8) and IRF5. Inhibition of P2X4R function suppresses neuropathic pain, indicating that microglial P2X4R play a key role in evoking neuropathic pain.
Lymphocyte recirculation between the blood and the lymphoid/non-lymphoid tissues is an essential homeostatic mechanism that regulates humoral and cellular immune responses in vivo. This system promotes the encounter of naïve T and B cells with their specific cognate antigen presented by dendritic cells, and with the regulatory cells with which they need to interact to initiate, maintain, and terminate immune responses. The constitutive lymphocyte trafficking is mediated by particular types of blood vessels, including the high endothelial venules (HEVs) in lymph nodes and Peyer’s patches, and the flat-walled venules in non-lymphoid tissues including the skin. The lymphocyte migration across HEVs involves tethering/rolling, arrest/firm adhesion/intraluminal crawling, and transendothelial migration. On the other hand, relatively little is known about how lymphocytes and other types of cells migrate across the venules of non-lymphoid tissues. Here we summarize recent findings about the molecular mechanisms that govern immune cell trafficking, including the roles of chemokines and lysophospholipids in regulating immune cell motility and endothelial permeability.
Chronic infection with Helicobacter pylori cagA-positive strains is the strongest risk factor of gastric cancer. The cagA gene-encoded CagA protein is delivered into gastric epithelial cells via bacterial type IV secretion, where it undergoes tyrosine phosphorylation at the Glu-Pro-Ile-Tyr-Ala (EPIYA) motifs. Delivered CagA then acts as a non-physiological scaffold/hub protein by interacting with multiple host signaling molecules, most notably the pro-oncogenic phosphatase SHP2 and the polarity-regulating kinase PAR1/MARK, in both tyrosine phosphorylation-dependent and -independent manners. CagA-mediated manipulation of intracellular signaling promotes neoplastic transformation of gastric epithelial cells. Transgenic expression of CagA in experimental animals has confirmed the oncogenic potential of the bacterial protein. Structural polymorphism of CagA influences its scaffold function, which may underlie the geographic difference in the incidence of gastric cancer. Since CagA is no longer required for the maintenance of established gastric cancer cells, studying the role of CagA during neoplastic transformation will provide an excellent opportunity to understand molecular processes underlying “Hit-and-Run” carcinogenesis.
Traditional breeding for high-yielding rice has been dependent on the widespread cultivation of gibberellin (GA)-deficient semi-dwarf varieties. Dwarfism lowers the “center of gravity” of the plant body, which increases resistance against lodging and enables plants to support high grain yield. Although this approach was successful in latter half of the 20th century in rice and wheat breeding, this may no longer be enough to sustain rice with even higher yields. This is because relying solely on the semi-dwarf trait is subject to certain limitations, making it necessary to use other important traits to reinforce it. In this review, we present an alternative approach to increase lodging resistance by improving the quality of the culm by identifying genes related to culm quality and introducing these genes into high-yielding rice cultivars through molecular breeding technique.
Even when the body is stationary, the whole retinal image is always in motion by fixational eye movements and saccades that move the eye between fixation points. Accumulating evidence indicates that the brain is equipped with specific mechanisms for compensating for the global motion induced by these eye movements. However, it is not yet fully understood how the retina processes global motion images during eye movements. Here we show that global motion images evoke novel coordinated firing in retinal ganglion cells (GCs). We simultaneously recorded the firing of GCs in the goldfish isolated retina using a multi-electrode array, and classified each GC based on the temporal profile of its receptive field (RF). A moving target that accompanied the global motion (simulating a saccade following a period of fixational eye movements) modulated the RF properties and evoked synchronized and correlated firing among local clusters of the specific GCs. Our findings provide a novel concept for retinal information processing during eye movements.