Non-cell-autonomous regulation of mTORC2 by Hedgehog signaling maintains lipid homeostasis.

Organisms allocate energetic resources between essential cellular processes to maintain homeostasis and, in turn, maximize fitness. The nutritional regulators of energy homeostasis have been studied in detail; however, how developmental signals might impinge on these pathways to govern metabolism is poorly understood. Here, we identify a non-canonical role for Hedgehog (Hh), a classic regulator of development, in maintaining intestinal lipid homeostasis in Caenorhabditis elegans.

A novel gain-of-function mutation in partially suppresses mTORC2 defects.

The serine/threonine protein kinase SGK-1 is a downstream target of mTOR complex 2 (mTORC2) and is a conserved regulator of growth and metabolism. In , mutations in , which encodes an essential component of mTORC2, impairs lipid homeostasis and growth; however, these defects are partially suppressed by an activating mutation in SGK-1 , E116K. Here, we describe a stronger gain-of-function mutation in , L112F, that was identified in a forward genetic screen for suppressor mutations This allele will be useful in further dissecting the mTORC2 pathway and provides new insight into the role of this conserved residue in regulating SGK-1 kinase activity.

The F-box protein FBXL-5 governs vitellogenesis and lipid homeostasis in .

The molecular mechanisms that govern the metabolic commitment to reproduction, which often occurs at the expense of somatic reserves, remain poorly understood. We identified the F-box protein FBXL-5 as a negative regulator of maternal provisioning of vitellogenin lipoproteins, which mediate the transfer of intestinal lipids to the germline. Mutations in partially suppress the vitellogenesis defects observed in the heterochronic mutants and both of which ectopically express at the adult developmental stage.

Non-cell-autonomous regulation of mTORC2 by Hedgehog signaling maintains lipid homeostasis.

Organisms must appropriately allocate energetic resources between essential cellular processes to maintain homeostasis and in turn, maximize fitness. The nutritional and homeostatic regulators of energy homeostasis have been studied in detail; however, how developmental signals might impinge on these pathways to govern cellular metabolism is poorly understood. Here, we identify a non-canonical role for Hedgehog (Hh), a classic regulator of development, in maintaining intestinal lipid homeostasis in .

The TWK-26 potassium channel governs nutrient absorption in the intestine.

Ion channels are necessary for proper water and nutrient absorption in the intestine, which supports cellular metabolism and organismal growth. While a role for Na co-transporters and pumps in intestinal nutrient absorption is well defined, how individual K uniporters function to maintain ion homeostasis is poorly understood. Using , we show that a gain-of-function mutation in , which encodes a two-pore domain K ion channel orthologous to human KCNK3, facilitates nutrient absorption and suppresses the metabolic and developmental defects displayed by impaired intestinal MAP Kinase (MAPK) signaling.

The F-box protein FBXL-5 governs vitellogenesis and lipid homeostasis in .

The molecular mechanisms that govern the metabolic commitment to reproduction, which often occurs at the expense of somatic reserves, remain poorly understood. We identified the F-box protein FBXL-5 as a negative regulator of maternal provisioning of vitellogenin lipoproteins, which mediate the transfer of intestinal lipids to the germline. Mutations in partially suppress the vitellogenesis defects observed in the heterochronic mutants and both of which ectopically express at the adult developmental stage.

Kombucha Tea-associated microbes remodel host metabolic pathways to suppress lipid accumulation.

The popularity of the ancient, probiotic-rich beverage Kombucha Tea (KT) has surged in part due to its purported health benefits, which include protection against metabolic diseases; however, these claims have not been rigorously tested and the mechanisms underlying host response to the probiotics in KT are unknown. Here, we establish a reproducible method to maintain C. elegans on a diet exclusively consisting of Kombucha Tea-associated microbes (KTM), which mirrors the microbial community found in the fermenting culture.

The mutation is a loss-of-function insertion within the locus.

The genes encoding the mitogen-activated protein kinases DRL-1 and FLR-4 are required for growth and lipid homeostasis in . Interestingly, the mutant, which was previously isolated in a forward genetic screen for mutations that confer fluoride resistance, phenocopies the and loss-of-function mutants; however, the genetic identity of is unknown. Through whole genome sequencing, we found that the mutation is an insertion in the locus and disrupts gene function, resulting in dramatic growth defects and impaired vitellogenin production.

Opposing action of the FLR-2 glycoprotein hormone and DRL-1/FLR-4 MAP kinases balance p38-mediated growth and lipid homeostasis in C. elegans.

Animals integrate developmental and nutritional signals before committing crucial resources to growth and reproduction; however, the pathways that perceive and respond to these inputs remain poorly understood. Here, we demonstrate that DRL-1 and FLR-4, which share similarity with mammalian mitogen-activated protein kinases, maintain lipid homeostasis in the C. elegans intestine.

Exploring the evolution and function of Canoe's intrinsically disordered region in linking cell-cell junctions to the cytoskeleton during embryonic morphogenesis.

One central question for cell and developmental biologists is defining how epithelial cells can change shape and move during embryonic development without tearing tissues apart. This requires robust yet dynamic connections of cells to one another, via the cell-cell adherens junction, and of junctions to the actin and myosin cytoskeleton, which generates force. The last decade revealed that these connections involve a multivalent network of proteins, rather than a simple linear pathway.

Exploring the evolution and function of Canoe’s intrinsically disordered region in linking cell-cell junctions to the cytoskeleton during embryonic morphogenesis.

One central question for cell and developmental biologists is defining how epithelial cells can change shape and move during embryonic development without tearing tissues apart. This requires robust yet dynamic connections of cells to one another, via the cell-cell adherens junction, and of junctions to the actin and myosin cytoskeleton, which generates force. The last decade revealed that these connections involve a multivalent network of proteins, rather than a simple linear pathway.

Binding specificity and function of the SWI/SNF subunit SMARCA4 bromodomain interaction with acetylated histone H3K14.

Bromodomains (BD) are conserved reader modules that bind acetylated lysine residues on histones. Although much has been learned regarding the in vitro properties of these domains, less is known about their function within chromatin complexes. SWI/SNF chromatin-remodeling complexes modulate transcription and contribute to DNA damage repair.

Maternal Inheritance: Longevity Programs Nourish Progeny via Yolk.

Epigenetic effects can be mediated by changes in chromatin state that are transmitted from parent to child via gametes, but support is gathering for maternal yolk, which is deposited into ooctyes, as an extranuclear epigenetic factor that can contribute to phenotypic plasticity across generations in Caenorhabditis elegans.

CEH-60/PBX and UNC-62/MEIS Coordinate a Metabolic Switch that Supports Reproduction in C. elegans.

The molecular basis of how animals integrate metabolic, developmental, and environmental information before committing resources to reproduction is an unresolved issue in developmental biology. In C. elegans, adult animals reallocate fat stores from intestinal cells to the germline via low-density lipoprotein (LDL)-like particles to promote embryogenesis.

A microRNA program in the C. elegans hypodermis couples to intestinal mTORC2/PQM-1 signaling to modulate fat transport.

Animals integrate metabolic, developmental, and environmental information before committing key resources to reproduction. In Caenorhabditis elegans, adult animals transport fat from intestinal cells to the germline to promote reproduction. We identified a microRNA (miRNA)-regulated developmental timing pathway that functions in the hypodermis to nonautonomously coordinate the mobilization of intestinal fat stores to the germline upon initiation of adulthood.

Aberrant Activation of p38 MAP Kinase-Dependent Innate Immune Responses Is Toxic to Caenorhabditis elegans.

Inappropriate activation of innate immune responses in intestinal epithelial cells underlies the pathophysiology of inflammatory disorders of the intestine. Here we examine the physiological effects of immune hyperactivation in the intestine of the nematode Caenorhabditis elegans. We previously identified an immunostimulatory xenobiotic that protects C.

Recognition of the protein kinase AVRPPHB SUSCEPTIBLE1 by the disease resistance protein RESISTANCE TO PSEUDOMONAS SYRINGAE5 is dependent on s-acylation and an exposed loop in AVRPPHB SUSCEPTIBLE1.

The recognition of pathogen effector proteins by plants is typically mediated by intracellular receptors belonging to the nucleotide-binding leucine-rich repeat (NLR) family. NLR proteins often detect pathogen effector proteins indirectly by detecting modification of their targets. How NLR proteins detect such modifications is poorly understood.

DAF-16 employs the chromatin remodeller SWI/SNF to promote stress resistance and longevity.

Organisms are constantly challenged by stresses and privations and require adaptive responses for their survival. The forkhead box O (FOXO) transcription factor DAF-16 (hereafter referred to as DAF-16/FOXO) is a central nexus in these responses, but despite its importance little is known about how it regulates its target genes. Proteomic identification of DAF-16/FOXO-binding partners in Caenorhabditis elegans and their subsequent functional evaluation by RNA interference revealed several candidate DAF-16/FOXO cofactors, most notably the chromatin remodeller SWI/SNF.

Widespread dynamic DNA methylation in response to biotic stress.

Regulation of gene expression by DNA methylation is crucial for defining cellular identities and coordinating organism-wide developmental programs in many organisms. In plants, modulation of DNA methylation in response to environmental conditions represents a potentially robust mechanism to regulate gene expression networks; however, examples of dynamic DNA methylation are largely limited to gene imprinting. Here we report an unexpected role for DNA methylation in regulation of the Arabidopsis thaliana immune system.

PIWI associated siRNAs and piRNAs specifically require the Caenorhabditis elegans HEN1 ortholog henn-1.

Small RNAs--including piRNAs, miRNAs, and endogenous siRNAs--bind Argonaute proteins to form RNA silencing complexes that target coding genes, transposons, and aberrant RNAs. To assess the requirements for endogenous siRNA formation and activity in Caenorhabditis elegans, we developed a GFP-based sensor for the endogenous siRNA 22G siR-1, one of a set of abundant siRNAs processed from a precursor RNA mapping to the X chromosome, the X-cluster. Silencing of the sensor is also dependent on the partially complementary, unlinked 26G siR-O7 siRNA.

Human DNA methylomes at base resolution show widespread epigenomic differences.

DNA cytosine methylation is a central epigenetic modification that has essential roles in cellular processes including genome regulation, development and disease. Here we present the first genome-wide, single-base-resolution maps of methylated cytosines in a mammalian genome, from both human embryonic stem cells and fetal fibroblasts, along with comparative analysis of messenger RNA and small RNA components of the transcriptome, several histone modifications, and sites of DNA-protein interaction for several key regulatory factors. Widespread differences were identified in the composition and patterning of cytosine methylation between the two genomes.

A family of bacterial cysteine protease type III effectors utilizes acylation-dependent and -independent strategies to localize to plasma membranes.

Bacterial phytopathogens employ a type III secretion system to deliver effector proteins into the plant cell to suppress defense pathways; however, the molecular mechanisms and subcellular localization strategies that drive effector function largely remain a mystery. Here, we demonstrate that the plant plasma membrane is the primary site for subcellular localization of the Pseudomonas syringae effector AvrPphB and five additional cysteine protease family members. AvrPphB and two AvrPphB-like effectors, ORF4 and NopT, autoproteolytically process following delivery into the plant cell to expose embedded sites for fatty acylation.

The phosphatase laforin crosses evolutionary boundaries and links carbohydrate metabolism to neuronal disease.

Lafora disease (LD) is a progressive myoclonic epilepsy resulting in severe neurodegeneration followed by death. A hallmark of LD is the accumulation of insoluble polyglucosans called Lafora bodies (LBs). LD is caused by mutations in the gene encoding the phosphatase laforin, which reportedly exists solely in vertebrates.

Erythropoietin protects cerebrocortical neurons from HIV-1/gp120-induced damage.

Infection with human immunodeficiency virus (HIV)-1 can lead to neurological complications that range from mild cognitive and motor impairment to HIV-associated dementia (HAD). The mechanism of brain injury and dementia remains poorly understood. Interestingly, post mortem brain specimen from HAD patients and transgenic mice expressing the viral envelope protein gp120 present with similar neuropathological signs.