Cinderella story: PI4P goes from precursor to key signaling molecule

Abstract

Phosphatidylinositol lipids are signaling molecules involved in nearly all aspects of cellular regulation. Production of phosphatidylinositol 4-phosphate (PI4P) has long been recognized as one of the first steps in generating poly-phosphatidylinositol phosphates involved in actin organization, cell migration, and signal transduction. In addition, progress over the last decade has brought to light independent roles for PI4P in membrane trafficking and lipid homeostasis. Here, we describe recent advances that reveal the breadth of processes regulated by PI4P, the spectrum of PI4P effectors, and the mechanisms of spatiotemporal control that coordinate crosstalk between PI4P and cellular signaling pathways.     

Propofol prevents lung injury after intestinal ischemia–reperfusion by inhibiting the interaction between mast cell activation and oxidative stress

Aims

Both mast cells and oxidative stress are involved in acute lung injury (ALI) induced by intestinal ischemia–reperfusion (IIR). The aim of this study was to investigate whether propofol could improve IIR-induced ALI through inhibiting their interaction.

Main methods

Repetitive, brief IIR or IIR + compound 48/80 was performed in adult Sprague–Dawley rats pretreated with saline, apocynin or propofol. And their lungs were excised for histology, ELISA and protein-expression measurements 2 h after reperfusion.

Key findings

Rats pretreated with saline developed critical ALI 2 h after IIR. We found significant elevations in lung injury scores, lung wet/dry ratio and gp91phox, p47phox, intercellular cell adhesion molecule-1 protein expressions and higher level of malondialdehyde, interleukin-6 contents, and myeloperoxidase activities, as well as significant reductions in superoxide dismutase activities, accompanied with increases in mast cell degranulation evidenced by significant increases in mast cell counts, β-hexosaminidase concentrations, and tryptase expression. And the lung injury was aggravated in the presence of compound 48/80. However, pretreated with propofol and apocynin not only ameliorated the IIR-mediated pulmonary changes beyond the biochemical changes but also reversed the changes that were aggravated by compound 48/80.

Significance

Propofol protects against IIR-mediated ALI, most likely by inhibiting the interaction between oxidative stress and mast cell degranulation.     

Phosphorylation of Pkp1 by RIPK4 regulates epidermal differentiation and skin tumorigenesis

Tissue homeostasis of skin is sustained by epidermal progenitor cells localized within the basal layer of the skin epithelium. Post‐translational modification of the proteome, such as protein phosphorylation, plays a fundamental role in the regulation of stemness and differentiation of somatic stem cells. However, it remains unclear how phosphoproteomic changes occur and contribute to epidermal differentiation. In this study, we survey the epidermal cell differentiation in a systematic manner by combining quantitative phosphoproteomics with mammalian kinome cDNA library screen. This approach identified a key signaling event, phosphorylation of a desmosome component, PKP1 (plakophilin‐1) by RIPK4 (receptor‐interacting serine–threonine kinase 4) during epidermal differentiation. With genome‐editing and mouse genetics approach, we show that loss of function of either Pkp1 or Ripk4 impairs skin differentiation and enhances epidermal carcinogenesis in vivo. Phosphorylation of PKP1's N‐terminal domain by RIPK4 is essential for their role in epidermal differentiation. Taken together, our study presents a global view of phosphoproteomic changes that occur during epidermal differentiation, and identifies RIPK‐PKP1 signaling as novel axis involved in skin stratification and tumorigenesis.     

Source-to-sink relationship between green leaves and green pseudobulbs of C<Subscript>3</Subscript> orchid in regulation of photosynthesis

In this paper, photosynthetic characteristics of green leaves (GL) and green pseudobulbs (GPSB) of C₃ orchid Oncidium Golden Wish were first studied. Light saturation for photosynthesis and maximum photosynthetic rates (P _max) were significantly higher in GL than in GPSB. The results of the optimal PSII quantum yield (F_v/F_m ratio), electron transport rate (ETR), the effective photochemical quantum yield (ΔF/F_m′) and nonphotochemical quenching (NPQ) of Chl fluorescence revealed that GPSB had lower light utilization than that of GL. Significantly higher photosynthetic pigments were found in GL than in GPSB. Alteration of source/sink ratio had no impact on all photosynthetic parameters for both GL and GPSB after a short term of 3 days or even a long term of 2 weeks of treatments although there were significant decreases in GL carbohydrate concentration of GL-darkened plants by the end of the day. However, decreases of all photosynthetic parameters of GL were observed in GL-darkened plants after 4 weeks of treatment compared to those of fully illuminated (FI) and GPSB-darkened plants. These results indicate that the level of carbohydrates in GL plays an important role in regulating their photosynthesis. Due to their lower photosynthetic capacities, GPSB function mainly as sinks. Darkening GPSB up to 2 weeks did not affect their own P _max and the P _max of GL and thus, did not result in significant decreases of total carbohydrate concentration of GPSB. As GPSB store a large amount of carbohydrates, it could also act as a source when the level of carbohydrates decreased. Thus, GL could depend on GPSB carbohydrates to regulate their photosynthesis when their source capacity was removed. However, 4 weeks after treatments, photosynthetic capacities of GL were significantly lower in GL- and GPSB-darkened plants than in FI plants, which could be due to the lower total soluble and insoluble sugar concentrations of both GL and GPSB in these plants.     

Hypoxia induces beta-amyloid in association with death of RGC-5 cells in culture

Beta-amyloid (Aβ) derived from amyloid precursor protein (APP) has been associated with retinal degeneration in Alzheimer’s disease (AD) and glaucoma. This study examined whether hypoxia exposure induces Aβ accumulation in RGC-5 cells. While levels of APP mRNA and protein significantly increased in the cells, elevated abundance of Aβ was also observed in cells and culture medium between 12 or 24 and 48 h after 5% O₂ hypoxia treatment. Additionally, there is a close relationship between induction of APP and Aβ and intracellular accumulation of ROS along with loss of mitochondrial membrane potential followed by the death of RGC-5 cells in culture under hypoxia. These results suggest a possible involvement of APP and Aβ in the death of RGCs challenged by hypoxia.     

分子标记育种在我国的研究进展

现代生物技术的发展为利用外源基因培育优良作物品种提供了新的途径。简要综述了分子标记育种在我国研究的总体情况以及我国在分子标记育种领域取得的成就,并对分子标记育种的前景进行了展望。