Auxin: a master regulator in plant root development

The demand for increased crop productivity and the predicted challenges related to plant survival under adverse environmental conditions have renewed the interest in research in root biology. Various physiological and genetic studies have provided ample evidence in support of the role of plant growth regulators in root development. The biosynthesis and transport of auxin and its signaling play a crucial role in controlling root growth and development. The univocal role of auxin in root development has established it as a master regulator. Other plant hormones, such as cytokinins, brassinosteroids, ethylene, abscisic acid, gibberellins, jasmonic acid, polyamines and strigolactones interact either synergistically or antagonistically with auxin to trigger cascades of events leading to root morphogenesis and development. In recent years, the availability of biological resources, development of modern tools and experimental approaches have led to the advancement of knowledge in root development. Research in the areas of hormone signal perception, understanding network of events involved in hormone action and the transport of plant hormones has added a new dimension to root biology. The present review highlights some of the important conceptual developments in the interplay of auxin and other plant hormones and associated downstream events affecting root development.     

The BLOC-1 complex promotes endosomal maturation by recruiting the Rab5 GTPase-activating protein Msb3

Membrane microcompartments of the early endosomes serve as a sorting and signaling platform, where receptors are either recycled back to the plasma membrane or forwarded to the lysosome for destruction. In metazoan cells, three complexes, termed BLOC-1 to -3, mediate protein sorting from the early endosome to lysosomes and lysosome-related organelles. We now demonstrate that BLOC-1 is an endosomal Rab-GAP (GTPase-activating protein) adapter complex in yeast. The yeast BLOC-1 consisted of six subunits, which localized interdependently to the endosomes in a Rab5/Vps21-dependent manner. In the absence of BLOC-1 subunits, the balance between recycling and degradation of selected cargoes was impaired. Additionally, our data show that BLOC-1 is both a Vps21 effector and an adapter for its GAP Msb3. BLOC-1 and Msb3 interacted in vivo, and both mutants resulted in a redistribution of active Vps21 to the vacuole surface. We thus conclude that BLOC-1 controls the lifetime of active Rab5/Vps21 and thus endosomal maturation along the endocytic pathway.     

A Model of the Membrane-bound Cytochrome b5-Cytochrome P450 Complex from NMR and Mutagenesis Data

Microsomal cytochrome b₅ (cytb₅) is a membrane-bound protein that modulates the catalytic activity of its redox partner, cytochrome P4502B4 (cytP450). Here, we report the first structure of full-length rabbit ferric microsomal cytb₅ (16 kDa), incorporated in two different membrane mimetics (detergent micelles and lipid bicelles). Differential line broadening of the cytb₅ NMR resonances and site-directed mutagenesis data were used to characterize the cytb₅ interaction epitope recognized by ferric microsomal cytP450 (56 kDa). Subsequently, a data-driven docking algorithm, HADDOCK (high ambiguity driven biomolecular docking), was used to generate the structure of the complex between cytP4502B4 and cytb₅ using experimentally derived restraints from NMR, mutagenesis, and the double mutant cycle data obtained on the full-length proteins. Our docking and experimental results point to the formation of a dynamic electron transfer complex between the acidic convex surface of cytb₅ and the concave basic proximal surface of cytP4502B4. The majority of the binding energy for the complex is provided by interactions between residues on the C-helix and β-bulge of cytP450 and residues at the end of helix α4 of cytb₅. The structure of the complex allows us to propose an interprotein electron transfer pathway involving the highly conserved Arg-125 on cytP450 serving as a salt bridge between the heme propionates of cytP450 and cytb₅. We have also shown that the addition of a substrate to cytP450 likely strengthens the cytb₅-cytP450 interaction. This study paves the way to obtaining valuable structural, functional, and dynamic information on membrane-bound complexes.     

The Peptidyl-prolyl Isomerase Pin1 Up-regulation and Proapoptotic Function in Dopaminergic Neurons: RELEVANCE TO THE PATHOGENESIS OF PARKINSON DISEASE*

Parkinson disease (PD) is a chronic neurodegenerative disease characterized by a slow and progressive degeneration of dopaminergic neurons in substantia nigra. The pathophysiological mechanisms underlying PD remain unclear. Pin1, a major peptidyl-prolyl isomerase, has recently been associated with certain diseases. Notably, Ryo et al. (Ryo, A., Togo, T., Nakai, T., Hirai, A., Nishi, M., Yamaguchi, A., Suzuki, K., Hirayasu, Y., Kobayashi, H., Perrem, K., Liou, Y. C., and Aoki, I. (2006) J. Biol. Chem. 281, 4117–4125) implicated Pin1 in PD pathology. Therefore, we sought to systematically characterize the role of Pin1 in PD using cell culture and animal models. To our surprise we observed a dramatic up-regulation of Pin1 mRNA and protein levels in dopaminergic MN9D neuronal cells treated with the parkinsonian toxicant 1-methyl-4-phenylpyridinium (MPP⁺) as well as in the substantia nigra of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model. Notably, a marked expression of Pin1 was also observed in the substantia nigra of human PD brains along with a high co-localization of Pin1 within dopaminergic neurons. In functional studies, siRNA-mediated knockdown of Pin1 almost completely prevented MPP⁺-induced caspase-3 activation and DNA fragmentation, indicating that Pin1 plays a proapoptotic role. Interestingly, multiple pharmacological Pin1 inhibitors, including juglone, attenuated MPP⁺-induced Pin1 up-regulation, α-synuclein aggregation, caspase-3 activation, and cell death. Furthermore, juglone treatment in the MPTP mouse model of PD suppressed Pin1 levels and improved locomotor deficits, dopamine depletion, and nigral dopaminergic neuronal loss. Collectively, our findings demonstrate for the first time that Pin1 is up-regulated in PD and has a pathophysiological role in the nigrostriatal dopaminergic system and suggest that modulation of Pin1 levels may be a useful translational therapeutic strategy in PD.     

Niche Partition of Bacteriovorax Operational Taxonomic Units Along Salinity and Temporal Gradients in the Chesapeake Bay Reveals Distinct Estuarine Strains

The predatory Bacteriovorax are Gram-negative bacteria ubiquitous in saltwater systems that prey upon other Gram-negative bacteria in a similar manner to the related genus Bdellovibrio. Among the phylogenetically defined clusters of Bacteriovorax, cluster V has only been isolated from estuaries suggesting that it may be a distinct estuarine phylotype. To assess this hypothesis, the spatial and temporal distribution of cluster V and other Bacteriovorax phylogenetic assemblages along the salinity gradient of Chesapeake Bay were determined. Cluster V was expected to be found in significantly greater numbers in low to moderate salinity waters compared to high salinity areas. The analyses of water and sediment samples from sites in the bay revealed cluster V to be present at the lower salinity and not high salinity sites, consistent with it being an estuarine phylotype. Cluster IV had a similar distribution pattern and may also be specifically adapted to estuaries. While the distribution of clusters V and IV were similar for salinity, they were distinct on temperature gradients, being found in cooler and in warmer temperatures, respectively. The differentiation of phylotype populations along the salinity and temporal gradients in Chesapeake Bay revealed distinct niches inhabited by different phylotypes of Bacteriovorax and unique estuarine phylotypes.     

Prevalence of MTHFR C677T Single Nucleotide Polymorphism in Genetically Isolated Populations in Jordan

Methylenetetrahydrofolate reductase (MTHFR) C677T single nucleotide polymorphism is a major inherited risk factor of venous thromboembolism. We sought to determine its prevalence in genetically isolated populations of Chechens and Circassians in Jordan. The MTHFR C677T mutation was analyzed from blood samples taken from 120 random unrelated Chechens and 72 Circassians. The prevalence of the MTHFR mutation in the Chechen population was 27.5% (allele frequency 15%); the prevalence among the Circassians was 50% (allele frequency 29.2%). The prevalence in the Chechen population is similar to that in Jordan and other world populations, but it is higher in the Circassian population. This study will contribute to understanding the interaction between genetic and environmental risk factors underlying thrombosis and will be useful in deciding which genetic variants should be tested in a clinical genetic testing service.     

Syntheses of lipophilic chalcones and their conformationally restricted analogues as antitubercular agents

Lipophilic chalcones and their conformationally restricted analogues were synthesized and evaluated for their antitubercular efficacy against Mycobacterium tuberculosis H37Rv strain. Compounds 16, 24, 25a and 25c were found to be active MIC at 60, 30, 3.5 and 7.5 μg-mL^?1. In vitro cytotoxicity of compounds 16, 24, 25a, 25c and 26 in non-cancerous human epithelial kidney cell line (HEK-293) showed that most active compound 25a was approximately 2.85 times selective towards tubercular versus healthy cells whereas compound 24 was found to be 16 times selective.     

Cinnamic acid induced changes in reactive oxygen species scavenging enzymes and protein profile in maize (Zea mays L.) plants grown under salt stress

Plant growth and development are greatly affected due to changes in environmental conditions and become a serious challenge to scientific people. Therefore, present study was conducted to determine the role of secondary metabolites on the growth and development of maize under abiotic stress conditions. Cinnamic acid (CA) is one of the basic phenylpropanoid with antioxidant activity, produced by plants in response to stressful conditions. Response of maize seeds to the presoaking treatment with 0.5 mM CA was studied under different concentrations of NaCl stress. Exogenous CA increased growth characteristics in saline and non-saline conditions, while effects of CA were more significant under saline conditions in comparison to non-saline conditions in maize plants. CA also reduced oxidative damage through the induction of ROS scavenging enzymes such as supperoxide dismutase (SOD) (EC 1.15.1.1), peroxidase (POD) (EC 1.11.1.7), while the activity of enzyme catalase (CAT) (EC 1.11.1.6) was decreased. The content of malondialdehyde (MDA) was reduced significantly in maize leaf under CA treatment. Changes in protein banding patterns in the maize leaves showed a wide variation in response to NaCl-stress, while in the presence of CA salt-induced expression of polypeptides was reduced significantly. Present study clearly reports the alleviative effects of CA in response to salinity stress on growth, metabolic activity and changes in protein profile of 21 days old maize plants.