We isolated a recessive Arabidopsis mutant, ctr1, that constitutively exhibits seedling and adult phenotypes observed in plants treated with the plant hormone ethylene. The ctr1 adult morphology can be phenocopied by treatment of wild-type plants with exogenous ethylene and is due, at least in part, to inhibition of cell elongation. Seedlings and adult ctr1 plants show constitutive expression of ethylene-regulated genes. The epistasis of ctr1 and other ethylene response mutants has defined the position of CTR1 in the ethylene signal transduction pathway. The CTR1 gene has been cloned, and the DNA sequences of four mutant alleles were determined. The gene encodes a putative serine/threonine protein kinase that is most closely related to the Raf protein kinase family.

Ethylene regulates plant growth, development, and responsiveness to a variety of stresses. Cloning of the Arabidopsis EIN2 gene identifies a central component of the ethylene signaling pathway. The amino-terminal integral membrane domain of EIN2 shows similarity to the disease-related Nramp family of metal-ion transporters. Expression of the EIN2 CEND is sufficient to constitutively activate ethylene responses and restores responsiveness to jasmonic acid and paraquat-induced oxygen radicals to mutant plants. EIN2 is thus recognized as a molecular link between previously distinct hormone response pathways. Plants may use a combinatorial mechanism for assessing various stresses by enlisting a common set of signaling molecules.

Mutations in the Arabidopsis ETHYLENE-INSENSITIVE3 (EIN3) gene severely limit a plant's response to the gaseous hormone ethylene. ein3 mutants show a loss of ethylene-mediated effects including gene expression, the triple response, cell growth inhibition, and accelerated senescence. EIN3 acts downstream of the histidine kinase ethylene receptor, ETR1, and the Raf-like kinase, CTR1. The EIN3 gene encodes a novel nuclear-localized protein that shares sequence similarity, structural features, and genetic function with three EIN3-LIKE (EIL) proteins. In addition to EIN3, EIL1 orEIL2 were able to complement ein3, suggesting their participation in the ethylene signaling pathway. Overexpression of EIN3 or EIL1 in wild-type or ethylene-insensitive2 plants conferred constitutive ethylene phenotypes, indicating their sufficiency for activation of the pathway in the absence of ethylene.

We have developed a method for turning on and off the expression of transgenes within Drosophila in both time and space. Two different enhancer detector elements carrying an RU486-inducible form of the yeast transcription factor GAL4 were constructed and used to generate enhancer detector lines. These lines were screened for RU486-inducible reporter gene expression in the adult head. We identified lines that exhibit inducible expression in many cell and tissue types, verifying that the elements respond to nearby enhancers. No expression was detected in the absence of the ligand. The P{Switch1} element responded to genomic enhancers less efficiently than P{Switch2} but produced more specific patterns of expression. Two P{Switch} lines were used to ablate fat body tissue in adult females through the induced expression of diphtheria toxin. These females were sterile, which correlates with fat body loss, and they died prematurely.

Smell is an ancient sensory system present in organisms from bacteria to humans. In the nematode Caeonorhabditis elegans , gustatory and olfactory neurons regulate aging and longevity. Using the fruit fly, Drosophila melanogaster , we showed that exposure to nutrient-derived odorants can modulate life span and partially reverse the longevity-extending effects of dietary restriction. Furthermore, mutation of odorant receptor Or83b resulted in severe olfactory defects, altered adult metabolism, enhanced stress resistance, and extended life span. Our findings indicate that olfaction affects adult physiology and aging in Drosophila , possibly through the perceived availability of nutritional resources, and that olfactory regulation of life span is evolutionarily conserved.

Memory and associated plasticity mechanisms span different timescales, from fleeting to enduring. This study shows that, across species, mTORC2's control of actin dynamics is critical for long-term forms of memory and synaptic plasticity. A major goal of biomedical research is the identification of molecular and cellular mechanisms that underlie memory storage. Here we report a previously unknown signaling pathway that is necessary for the conversion from short- to long-term memory. The mammalian target of rapamycin (mTOR) complex 2 (mTORC2), which contains the regulatory protein Rictor (rapamycin-insensitive companion of mTOR), was discovered only recently and little is known about its function. We found that conditional deletion of Rictor in the postnatal murine forebrain greatly reduced mTORC2 activity and selectively impaired both long-term memory (LTM) and the late phase of hippocampal long-term potentiation (L-LTP). We also found a comparable impairment of LTM in dTORC2-deficient flies, highlighting the evolutionary conservation of this pathway. Actin polymerization was reduced in the hippocampus of mTORC2-deficient mice and its restoration rescued both L-LTP and LTM. Moreover, a compound that promoted mTORC2 activity converted early LTP into late LTP and enhanced LTM. Thus, mTORC2 could be a therapeutic target for the treatment of cognitive dysfunction.