Arabidopsis RTNLB1 and RTNLB2 Reticulon-Like Proteins Regulate Intracellular Trafficking and Activity of the FLS2 Immune Receptor[C][W]
This study finds that two reticulon proteins modulate the transport of an immune receptor to the cell membrane. The results highlight the role of receptor secretion in determining the receptor’s forward signaling efficacy and the cell’s response. Receptors localized at the plasma membrane are critical for the recognition of pathogens. The molecular determinants that regulate receptor transport to the plasma membrane are poorly understood. In a screen for proteins that interact with the FLAGELIN-SENSITIVE2 (FLS2) receptor using Arabidopsis thaliana protein microarrays, we identified the reticulon-like protein RTNLB1. We showed that FLS2 interacts in vivo with both RTNLB1 and its homolog RTNLB2 and that a Ser-rich region in the N-terminal tail of RTNLB1 is critical for the interaction with FLS2. Transgenic plants that lack RTNLB1 and RTNLB2 (rtnlb1 rtnlb2) or overexpress RTNLB1 (RTNLB1ox) exhibit reduced activation of FLS2-dependent signaling and increased susceptibility to pathogens. In both rtnlb1 rtnlb2 and RTNLB1ox, FLS2 accumulation at the plasma membrane was significantly affected compared with the wild type. Transient overexpression of RTNLB1 led to FLS2 retention in the endoplasmic reticulum (ER) and affected FLS2 glycosylation but not FLS2 stability. Removal of the critical N-terminal Ser-rich region or either of the two Tyr-dependent sorting motifs from RTNLB1 causes partial reversion of the negative effects of excess RTNLB1 on FLS2 transport out of the ER and accumulation at the membrane. The results are consistent with a model whereby RTNLB1 and RTNLB2 regulate the transport of newly synthesized FLS2 to the plasma membrane.

title: Secretory Low Molecular Weight Phospholipase A2 Plays Important Roles in Cell Elongation and Shoot Gravitropism in Arabidopsis Article, publication date, and citation information can be found at www.plantcell.org/cgi/doi/10.1105/tpc.014423.
abstract: To elucidate the cellular functions of phospholipase A2 in plants, an Arabidopsis cDNA encoding a secretory low molecular weight phospholipase A2 (AtsPLA2β) was isolated. Phenotype analyses of transgenic plants showed that overexpression of AtsPLA2β promotes cell elongation, resulting in prolonged leaf petioles and inflorescence stems, whereas RNA interference–mediated silencing of AtsPLA2β expression retards cell elongation, resulting in shortened leaf petioles and stems. AtsPLA2β is expressed in the cortical, vascular, and endodermal cells of the actively growing tissues of inflorescence stems and hypocotyls. AtsPLA2β then is secreted into the extracellular spaces, where signaling for cell wall acidification is thought to occur. AtsPLA2β-overexpressing or -silenced transgenic plants showed altered gravitropism in inflorescence stems and hypocotyls. AtsPLA2β expression is induced rapidly by auxin treatment and in the curving regions of inflorescence stems undergoing the gravitropic response. These results suggest that AtsPLA2β regulates the process of cell elongation and plays important roles in shoot gravitropism by mediating auxin-induced cell elongation.

title: Multiple forms of secretory phospholipase A2 in plants.
abstract: Multiple secretory phospholipase A2 (sPLA2) genes have been identified in plants and encode isoforms with distinct regulatory and catalytic properties. Elucidation of this genetic and biochemical heterogeneity has provided important clues to the regulation and function of the individual enzymes. An increasing body of evidence shows that their lipid products, lysophospholipids and free fatty acids, mediate a variety of cellular responses, including plant growth, development, and responses to stress and defense. This review discusses the newly-acquired information on plant sPLA2s including the molecular and biochemical characteristics, and signaling functions of each isoform.

title: FOXO3a turns the tumor necrosis factor receptor signaling towards apoptosis through reciprocal regulation of c-Jun N-terminal kinase and NF-kappaB.
abstract: We evaluated the full range effects of FOXO3a in endothelial cells (ECs) by microarray analysis and investigated the role of FOXO3a regulating TNF receptor signaling pathway.



Human umbilical vein endothelial cells (HUVECs) were transfected with adenoviral vectors expressing constitutively active FOXO3a (Ad-TM-FOXO3a). Ad-TM-FOXO3a transfection caused remarkable apoptosis, which were accompanied with upregulation of genes related with TNF receptor signaling, such as TNF-alpha, TANK (TRAF-associated NF-kappaB activator), and TTRAP (TRAF and TNF receptor-associated protein). Furthermore, kappaB-Ras1 (IkappaB-interacting Ras-like protein-1) which is known to block IkappaB degradation was found increased, and intranuclear translocation of NF-kappaB was inhibited. GADD45beta and XIAP, negative regulators of c-Jun N-terminal kinase (JNK), were suppressed and JNK activity was increased. Attenuation of TNF signaling pathway either by blocking antibody for TNF receptor or by blocking JNK with DMAP (6-dimethylaminopurine) or Ad-TAM67 (dominant negative c-Jun) cotransfection, significantly reduced FOXO3a-induced apoptosis. Finally, treatment of vasculature with heat shock, an activator of endogenous FOXO3a, resulted in EC apoptosis, which was completely rescued by Ad-TAM67.



FOXO3a promotes apoptosis of ECs, through activation of JNK and suppression of NF-kappaB. These data identify a novel role of FOXO3a to turn TNF receptor signaling to a proapoptotic JNK-dependent pathway.

title: Development of tripeptidyl farnesyltransferase inhibitors.
abstract: The first example of tripeptide inhibitors of farnesyltransferase with sub-micromolar inhibition activity was developed based on the fact that CVFM is not a substrate for farnesyltransferase.

title: Oral mucous membrane pemphigoid: complete response to topical tacrolimus.
abstract: Mucous membrane pemphigoid includes a heterogeneous group of blistering diseases, which have in common the involvement of the mucosae, a chronic course and a scarring tendency (1–3). The oral mucosa, conjunctiva, and, less frequently, the nose, oesophagus, larynx and genitals may be affected (1–3). Erosions and scarring of the mucosae might result in significant morbidity, and treatment is usually challenging. We report here a case of oral mucous membrane pemphigoid that was treated successfully with oral rinses of topical tacrolimus.

title: Differential roles of human Dicer-binding proteins TRBP and PACT in small RNA processing
abstract: During RNA interference and related gene regulatory pathways, the endonuclease Dicer cleaves precursor RNA molecules to produce microRNAs (miRNAs) and short interfering RNAs (siRNAs). Human cells encode a single Dicer enzyme that can associate with two different double-stranded RNA (dsRNA)-binding proteins, protein activator of PKR (PACT) and trans-activation response RNA-binding protein (TRBP). However, the functional redundancy or differentiation of PACT and TRBP in miRNA and siRNA biogenesis is not well understood. Using a reconstituted system, we show here that PACT and TRBP have distinct effects on Dicer-mediated dsRNA processing. In particular, we found that PACT in complex with Dicer inhibits the processing of pre-siRNA substrates when compared with Dicer and a Dicer–TRBP complex. In addition, PACT and TRBP show non-redundant effects on the production of different-sized miRNAs (isomiRs), which in turn alter target-binding specificities. Experiments using chimeric versions of PACT and TRBP suggest that the two N-terminal RNA-binding domains of each protein confer the observed differences in dsRNA substrate recognition and processing behavior of Dicer–dsRNA-binding protein complexes. These results support the conclusion that in humans, Dicer-associated dsRNA-binding proteins are important regulatory factors that contribute both substrate and cleavage specificity during miRNA and siRNA production.

title: Musical training effect on reading musical notation: evidence from event-related potentials.
abstract: Musical training enhances a range of non-musical cognitive functions, including visuospatial abilities. The aim of this study was to explore which event-related potential (ERP) components were enhanced or reduced as a result of musical training. Both electrophysiological and behavioral methods were used to compare musicians and non-musicians in the processing of pitch and duration when reading single musical notes. It was observed that in the early stage of note reading, the musician/non-musician differences emerged in the latency range of the N1 and N2. The N1 component was enhanced; in contrast, the N2 component was reduced in musicians. It is possible that musicians receive auditory meanings from visual music notations, so they therefore did not find it necessary to spend more resources on executing spatial attention than non-musicians do during pitch processing.