Contents of Volume 53

Plant Molecular Biology -     

Substrate Selectivity of Lysophospholipid Transporter LplT Involved in Membrane Phospholipid Remodeling in Escherichia coli

Lysophospholipid transporter (LplT) was previously found to be primarily involved in 2-acyl lysophosphatidylethanolamine (lyso-PE) recycling in Gram-negative bacteria. This work identifies the potent role of LplT in maintaining membrane stability and integrity in the Escherichia coli envelope. Here we demonstrate the involvement of LplT in the recycling of three major bacterial phospholipids using a combination of an in vitro lysophospholipid binding assay using purified protein and transport assays with E. coli spheroplasts. Our results show that lyso-PE and lysophosphatidylglycerol, but not lysophosphatidylcholine, are taken up by LplT for reacylation by acyltransferase/acyl-acyl carrier protein synthetase on the inner leaflet of the membrane. We also found a novel cardiolipin hydrolysis reaction by phospholipase A₂ to form diacylated cardiolipin progressing to the completely deacylated headgroup. These two distinct cardiolipin derivatives were both translocated with comparable efficiency to generate triacylated cardiolipin by acyltransferase/acyl-acyl carrier protein synthetase, demonstrating the first evidence of cardiolipin remodeling in bacteria. These findings support that a fatty acid chain is not required for LplT transport. We found that LplT cannot transport lysophosphatidic acid, and its substrate binding was not inhibited by either orthophosphate or glycerol 3-phosphate, indicating that either a glycerol or ethanolamine headgroup is the chemical determinant for substrate recognition. Diacyl forms of PE, phosphatidylglycerol, or the tetra-acylated form of cardiolipin could not serve as a competitive inhibitor in vitro. Based on an evolutionary structural model, we propose a “sideways sliding” mechanism to explain how a conserved membrane-embedded α-helical interface excludes diacylphospholipids from the LplT binding site to facilitate efficient flipping of lysophospholipid across the cell membrane.     

Peptidome analysis reveals the involvement of endogenous peptides in mouse pancreatic dysfunction with aging

Type 2 diabetes (T2D) is a glucose regulation disorder that has significantly enhanced mortality and the global disease burden. The prevalence of T2D has increased worldwide and is higher in the elderly. The function of pancreatic islets decreases with age, which is one important reason for the occurrence of diabetes in the elderly. Recently, peptidome analysis has attracted attention. However, the role of age-related peptides in pancreatic dysfunction has not been investigated extensively. Here, we conducted a comparison of endogenous peptides between pancreas from adult and aging mice by liquid chromatography tandem mass spectrometry (LC-MS/MS). A total of 2,089 peptides originating from 1,280 protein precursors were identified, of which 232 were upregulated and 183 were downregulated in the aging mice (fold change ≥ 2 and p < 0.05), suggesting that the expression of pancreatic peptides in mice varied with age. The molecular weight of most peptides was <3.0 kDa, and the isoelectric point distribution had a bimodal characteristic. Further analysis of cleavage site patterns indicated that proteases cleaved pancreatic proteins according to their rules. Moreover, Gene Ontology and pathway analyses showed that the differentially expressed peptides potentially had specific effects on pancreatic dysfunction. Some differential peptides were located within the domains of precursor proteins that were closely associated with the development of diabetes. We believe that our research may advance the current understanding of pancreas-derived peptides and that certain peptides may be involved in the etiology of diabetes.     

Erratum to: Overdose the addiction—A new strategy to ablate cancer cells

正The figure legend mistakenly referred to Reference 3 instead of Reference 1.It should read:"Adapted from Hu et al.[1]with permission from the authors."The author apologizes for any inconvenience it might have caused.     

Comparative embryogenesis of Mecoptera and Lepidoptera with special reference to the abdominal prolegs

The eruciform larvae of holometabolous insects are primarily characterized by bearing a varying number of abdominal prolegs in addition to three pairs of thoracic legs. However, whether the prolegs are evolutionarily homologous among different insect orders is still a disputable issue. We examined the embryonic features and histological structure of the prolegs of the scorpionfly Panorpa byersi Hua and Huang (Mecoptera: Panorpidae) and the Oriental armyworm Mythimna separata (Walker) (Lepidoptera: Noctuidae) to investigate whether the prolegs are homologous between these two holometabolous insect orders. In the scorpionfly, paired lateral process primordia arise on abdominal segments I–VIII (A1–A8) in line with the thoracic legs in early embryonic stages, but degenerate into triangular protuberances in later stages, and paired medial processes appear along the midventral line before dorsal closure and eventually develop into unjointed, cone‐shaped prolegs. Histological observation showed that the lumina of the prolegs are not continuous with the hemocoel, differing distinctly from that of the basic appendicular plan of thoracic legs. These results suggest that the prolegs are likely secondary outgrowths in Mecoptera. In the armyworm, lateral process primordia appear on A1–A10 in alignment with the thoracic legs in the early embryonic stages, although only the rudiments on A3–A6 and A10 develop into segmented prolegs with the lumina continuous with the hemocoel and others degenerate eventually, suggesting that the prolegs are true segmental appendages serially homologous with the thoracic legs in Lepidoptera. Therefore, we conclude that the larval prolegs are likely not evolutionarily homologous between Mecoptera and Lepidoptera. J. Morphol. 277:585–593, 2016. © 2016 Wiley Periodicals, Inc.     

The 2015 Albert Lasker Basic Medical Research Award: An exhilarating journey to the DNA damage checkpoint

正The field of DNA damage response has experienced an extraordinary year in 2015.The Lasker Award in Basic Medical Research recognized Drs.Evelyn Witkin and Stephen J.Elledge for their groundbreaking works in the DNA damage response,followed by the Nobel Chemistry Prize honoring three pioneers in DNA damage repair.These highest awards     

Monte Carlo Simulation-Based Health Risk Assessment of Heavy Metal Soil Pollution: A Case Study in the Qixia Mining Area,China

In recent years, heavy metal pollution accidents have occurred in many regions of China, and the public has become increasingly concerned about its health. Based on a U.S. Environmental Protection Agency model and using Monte Carlo simulation techniques, this article presents a procedure for health risk assessment of heavy metal pollution. A case study was conducted in the Qixia lead and zinc mining area. Based on the magnitude of heavy metal contamination in the mine factory, vicinal Qixia scenic site and village, the potential health risk calculated for a lifetime of exposure (through ingestion and dermal contact) was determined as the cumulative carcinogenic and non-carcinogenic risk for workers, tourists, and local residents (including children and adults), respectively. The risk assessment indicated that the carcinogenic risk is not significant. However, Pb poses a significant cumulative non-carcinogenic risk, which tends to be serious for workers. Additionally, local children are more vulnerable than adults to the risks associated with heavy metal contamination. Accordingly, risk alleviation and preventive measures should be taken, especially for children and workers.     

The NLR protein,NLRX1, and its partner,TUFM, reduce type I interferon,and enhance autophagy

The NLR (nucleotide-binding domain leucine-rich repeat containing) proteins serve as regulators of inflammatory signaling pathways. NLRX1, a mitochondria-localized NLR protein, has been previously shown to negatively regulate inflammatory cytokine production activated via the MAVS-DDX58 (RIG-I) pathway. The literature also indicates that DDX58 has a negative impact upon autophagy. Consistent with the inhibitory role of NLRX1 on DDX58, our recent study indicates a role of NLRX1 in augmenting virus-induced autophagy. This effect is through its interaction with another mitochondrial protein TUFM (Tu translation elongation factor, mitochondrial, also known as EF-TuMT, COXPD4, and P43). TUFM also reduces DDX58-activated cytokines but augments autophagy. Additionally it interacts with ATG12–ATG5-ATG16L1 to form a molecular complex that modulates autophagy. The work shows that both NLRX1 and TUFM work in concert to reduce cytokine response and augment autophagy.