Atamian H.S.,Graduate Program in Genetics |
Chaudhary R.,Graduate Program in Genetics |
Girke T.,Graduate Program in Genetics |
Kaloshian I.,Graduate Program in Genetics |
Kaloshian I.,University of California at Riverside
Molecular Plant-Microbe Interactions | Year: 2013
The interactions between aphids and their host plants seem to be analogous to those of plant-microbial pathogens. Unlike microbial pathogen effectors, little is known about aphid effectors and their ability to interfere with host immunity. To date, only three functional aphid effectors have been reported. To identify potato aphid (Macrosiphum euphorbiae) effectors, we developed a salivary gland transcriptome using Illumina technology. We generated 85 million Illumina reads from salivary glands and assembled them into 646 contigs. Ab initio sequence analysis predicted secretion signal peptides in 24% of these sequences, suggesting that they might be secreted into the plant during aphid feeding. Eight of these candidate effectors with secretion signal peptides were functionally characterized using Agrobacterium tumefaciens- mediated transient overexpression in Nicotiana benthamiana. Two candidate effectors, Me10 and Me23, increased aphid fecundity, suggesting their ability to suppress N. benthamiana defenses. Five of these candidate effectors, including Me10 and Me23, were also analyzed in tomato by delivering them through the Pseudomonas syringae type three secretion system. In tomato, only Me10 increased aphid fecundity. This work identified two additional aphid effectors with ability to manipulate the host for their advantage. © 2013 The American Phytopathological Society.
Sun S.,University of Texas Southwestern Medical Center |
Lourie R.,Materials Medical Research Institute |
Goodrich J.K.,Graduate Program in Genetics |
Poole A.C.,Cornell University |
And 5 more authors.
Molecular Biology of the Cell | Year: 2016
Inflammatory bowel disease (IBD) is an incurable chronic idiopathic disease that drastically decreases quality of life. Endoplasmic reticulum (ER)-associated degradation (ERAD) is responsible for the clearance of misfolded proteins; however, its role in disease pathogenesis remains largely unexplored. Here we show that the expression of SEL1L and HRD1, the most conserved branch of mammalian ERAD, is significantly reduced in ileal Crohn's disease (CD). Consistent with this observation, laboratory mice with enterocyte-specific Sel1L deficiency (Sel1LδIEC) develop spontaneous enteritis and have increased susceptibility to Toxoplasma gondii- induced ileitis. This is associated with profound defects in Paneth cells and a disproportionate increase of Ruminococcus gnavus, a mucolytic bacterium with known association with CD. Surprisingly, whereas both ER stress sensor IRE1α and effector CHOP are activated in the small intestine of Sel1LδIEC mice, they are not solely responsible for ERAD deficiency-associated lesions seen in the small intestine. Thus our study points to a constitutive role of Sel1L-Hrd1 ERAD in epithelial cell biology and the pathogenesis of intestinal inflammation in CD. © 2016 Sun et al.
PubMed | Graduate Program in Genetics, University of California at San Diego and University of California at Riverside
Type: Journal Article | Journal: Proceedings of the National Academy of Sciences of the United States of America | Year: 2014
Aphids are sap-feeding plant pests and harbor the endosymbiont Buchnera aphidicola, which is essential for their fecundity and survival. During plant penetration and feeding, aphids secrete saliva that contains proteins predicted to alter plant defenses and metabolism. Plants recognize microbe-associated molecular patterns and induce pattern-triggered immunity (PTI). No aphid-associated molecular pattern has yet been identified. By mass spectrometry, we identified in saliva from potato aphids (Macrosiphum euphorbiae) 105 proteins, some of which originated from Buchnera, including the chaperonin GroEL. Because GroEL is a widely conserved bacterial protein with an essential function, we tested its role in PTI. Applying or infiltrating GroEL onto Arabidopsis (Arabidopsis thaliana) leaves induced oxidative burst and expression of PTI early marker genes. These GroEL-induced defense responses required the known coreceptor BRASSINOSTEROID INSENSITIVE 1-ASSOCIATED RECEPTOR KINASE 1. In addition, in transgenic Arabidopsis plants, inducible expression of groEL activated PTI marker gene expression. Moreover, Arabidopsis plants expressing groEL displayed reduced fecundity of the green peach aphid (Myzus persicae), indicating enhanced resistance against aphids. Furthermore, delivery of GroEL into tomato (Solanum lycopersicum) or Arabidopsis through Pseudomonas fluorescens, engineered to express the type III secretion system, also reduced potato aphid and green peach aphid fecundity, respectively. Collectively our data indicate that GroEL is a molecular pattern that triggers PTI.
PubMed | Graduate Program in Genetics, University of California at Riverside and Southwest University
Type: Journal Article | Journal: Proceedings of the National Academy of Sciences of the United States of America | Year: 2014
Lineage-specific microRNAs (miRNAs) may contribute to functions specific to hematophagous mosquitoes and, as such, have potential for contributing to the development of future mosquito control approaches. Here we report that the mosquito- and gut-specific miRNA, miR-1174, is required for proper sugar absorption, fluid excretion, blood intake, and, consequently, egg maturation and survival in female mosquitoes. miR-1174 is highly expressed and localized in the posterior midgut, the blood-digesting portion of the mosquito alimentary canal. Depletion of miR-1174 results in severe defects in sugar absorption and blood intake. We identified serine hydroxymethyltransferase (SHMT) is a direct miR-1174 target. The adverse phenotypes caused by miR-1174 silencing were rescued by SHMT RNA interference. Our results suggest that miR-1174 is essential for fine-tuning the SHMT transcript to levels necessary for normal mosquito gut functions.
News Article | February 22, 2017
RIVERSIDE, Calif. - The mosquito Aedes aegypti, which can spread dengue fever, chikungunya, Zika fever, and yellow fever virus, requires a blood meal to develop eggs. One way to control the spread of these diseases is to tamper with the reproductive events that follow this mosquito's blood meal. This is what a team of scientists at the University of California, Riverside has explored at the molecular level. The researchers focused on small regulatory RNA molecules, called microRNAs, which play a critical role in mosquito egg maturation. They studied microRNA expression in the Aedes aegypti fat body--the metabolic center that plays a key role in reproduction. Since proper functioning of the fat body is essential for the development of the female reproductive system after a blood meal, identifying which miRNAs are important to fat body functions, and what specific genes they target, can help design ways to manipulate the levels of microRNA or their targets, affect their interactions, disrupt mosquito reproduction, and thus prevent the spread of diseases the mosquitoes transmit. The researchers report online this week in the Proceedings of the National Academy of Sciences that they observed five major microRNA expression peaks within a 48-hour period following the female mosquito's blood meal. "What we observed is that the levels of many miRNAs change significantly throughout the 48-hour period following a blood meal, indicating that these miRNAs, in turn, may be establishing significant changes in expression of key genes during this time in the fat body," said Fedor V. Karginov, an assistant professor of cell biology and neuroscience, who co-led the research team along with Alexander S. Raikhel, a distinguished professor of entomology at UC Riverside. "Our work has given us a much needed picture of which miRNAs are abundant in the fat body tissue, how each miRNA subgroup changes over time, and we have confirmation that specific up- and down-regulation of miRNA levels takes place during egg development." Specifically, the researchers measured the levels of all microRNAs in the fat body (around 100 different miRNAs) at five points of time, starting just before mosquitos take a blood meal, and then 6, 24, 36, and 48 hours after the blood meal. The timing of these was chosen based on previously known information on the timing of major physiological changes - or milestones - in the fat body after a blood meal. Karginov explained that each microRNA, together with a partner protein called Argonaute or "Ago," binds to (or "targets") several to many "messenger RNAs" (mRNAs), and thus down-regulates the expression of the corresponding genes. Determining the targets of important miRNAs is crucial to uncover the regulatory gene networks that drive the physiological changes in the fat body after blood meal. Karginov, Raikhel and their team members experimentally identified the binding sites for Ago/miRNAs on mRNAs in the fat body. They performed this identification at two points of time to study any changes that may have occurred, using "CLIP-seq," an experimentally challenging procedure that, to Karginov and his team's knowledge, has not been used on mosquito tissues before, and that provides a large trove of potential microRNA-mRNA interactions for further investigation. "The CLIP-seq data have given us insight into which genes the microRNA target, providing a solid foundation for future studies of miRNA regulation during the egg production cycle," Raikhel said. "Now that we know these genes, we are a step closer to controlling the spread of Aedes aegypti by disrupting a key process in the reproductive cycle: egg production." Karginov and Raikhel were joined in the research by Xiufeng Zhang (first author of the paper), a postdoctoral researcher in Raikhel's lab; Emre Aksoy, a second-year student in the Graduate Program in Genetics, Genomics and Bioinformatics; and Thomas Girke, a professor of bioinformatics. The study was supported by a grant from the National Institutes of Health. The University of California, Riverside is a doctoral research university, a living laboratory for groundbreaking exploration of issues critical to Inland Southern California, the state and communities around the world. Reflecting California's diverse culture, UCR's enrollment is now nearly 23,000 students. The campus opened a medical school in 2013 and has reached the heart of the Coachella Valley by way of the UCR Palm Desert Center. The campus has an annual statewide economic impact of more than $1 billion. A broadcast studio with fiber cable to the AT&T Hollywood hub is available for live or taped interviews. UCR also has ISDN for radio interviews. To learn more, call (951) UCR-NEWS.
Li F.-Q.,SUNY at Stony Brook |
Mofunanya A.,Graduate Program in Genetics |
Fischer V.,Graduate Program in Molecular and Cellular Pharmacology |
Hall J.,SUNY at Stony Brook |
Takemaru K.-I.,SUNY at Stony Brook
Molecular Biology of the Cell | Year: 2010
In the canonical Wnt pathway, β-catenin acts as a key coactivator that stimulates target gene expression through interaction with Tcf/Lef transcription factors. Its nuclear accumulation is the hallmark of active Wnt signaling and is frequently associated with cancers. Chibby (Cby) is an evolutionarily conserved molecule that represses β-catenin-dependent gene activation. Although Cby, in conjunction with 14-3-3 chaperones, controls β-catenin distribution, its molecular nature remains largely unclear. Here, we provide compelling evidence that Cby harbors bona fide nuclear localization signal (NLS) and nuclear export signal (NES) motifs, and constitutively shuttles between the nucleus and cytoplasm. Efficient nuclear export of Cby requires a cooperative action of the intrinsic NES, 14-3-3, and the CRM1 nuclear export receptor. Notably, 14-3-3 docking provokes Cby binding to CRM1 while inhibiting its interaction with the nuclear import receptor importin-α, thereby promoting cytoplasmic compartmentalization of Cby at steady state. Importantly, the NLS- and NES-dependent shuttling of Cby modulates the dynamic intracellular localization of β-catenin. In support of our model, short hairpin RNA-mediated knockdown of endogenous Cby results in nuclear accumulation of β-catenin. Taken together, these findings unravel the molecular basis through which a combinatorial action of Cby and 14-3-3 proteins controls the dynamic nuclear-cytoplasmic trafficking of β-catenin. © 2010 by The American Society for Cell Biology.