@article {1231, title = {A sleep-inducing gene, nemuri, links sleep and immune function in Drosophila [Transgenic Fly Facility]}, journal = {Science}, volume = {363}, year = {2019}, month = {2019 02 01}, pages = {509-515}, abstract = {

Sleep remains a major mystery of biology. In particular, little is known about the mechanisms that account for the drive to sleep. In an unbiased screen of more than 12,000 lines, we identified a single gene, , that induces sleep. The NEMURI protein is an antimicrobial peptide that can be secreted ectopically to drive prolonged sleep (with resistance to arousal) and to promote survival after infection. Loss of increased arousability during daily sleep and attenuated the acute increase in sleep induced by sleep deprivation or bacterial infection. Conditions that increase sleep drive induced expression of in a small number of fly brain neurons and targeted it to the sleep-promoting, dorsal fan-shaped body. We propose that NEMURI is a bona fide sleep homeostasis factor that is particularly important under conditions of high sleep need; because these conditions include sickness, our findings provide a link between sleep and immune function.

}, keywords = {Animals, Antimicrobial Cationic Peptides, Arousal, Bacterial Infections, Brain, Drosophila melanogaster, Drosophila Proteins, Female, Gain of Function Mutation, Gene Knockout Techniques, Homeostasis, Immune System, Male, Neurons, Sleep}, issn = {1095-9203}, doi = {10.1126/science.aat1650}, author = {Toda, Hirofumi and Williams, Julie A and Gulledge, Michael and Sehgal, Amita} } @article {476, title = {The E3 ligase ube3a is required for learning in Drosophila melanogaster. [Drosophila facility]}, journal = {Biochem Biophys Res Commun}, volume = {462}, year = {2015}, month = {2015 Jun 19}, pages = {71-7}, abstract = {

Angelman syndrome and autism are neurodevelopmental disorders linked to mutations and duplications of an E3 ligase called ube3a respectively. Since cognitive deficits and learning disabilities are hallmark symptoms of both these disorders, we investigated a role for dube3a in the learning ability of flies using the aversive phototaxis suppression assay. We show that down and up-regulation of dube3a are both detrimental to learning in larvae and adults. Using conditional gene expression we found that dube3a is required for normal brain development and during adulthood. Furthermore, we suggest that dube3a could be interacting with other learning and memory genes such as derailed. Along with firmly establishing dube3a as a gene that is required for learning, our work also opens avenues for further understanding the role played by this gene in brain development and behavior.

}, keywords = {Animals, Animals, Genetically Modified, Brain, Drosophila melanogaster, Drosophila Proteins, Gene Expression Regulation, Developmental, Immunoblotting, Larva, Learning, Memory, Motor Activity, Mushroom Bodies, Mutation, Reverse Transcriptase Polymerase Chain Reaction, Time Factors, Ubiquitin-Protein Ligases}, issn = {1090-2104}, doi = {10.1016/j.bbrc.2015.04.110}, author = {Chakraborty, Moumita and Paul, Blesson K and Nayak, Tanmoyita and Das, Aniruddha and Jana, Nihar R and Bhutani, Supriya} } @article {475, title = {Genetic transformation of structural and functional circuitry rewires the Drosophila brain. [Drosophila Facility]}, journal = {Elife}, volume = {3}, year = {2014}, month = {2014 Dec 29}, abstract = {

Acquisition of distinct neuronal identities during development is critical for the assembly of diverse functional neural circuits in the brain. In both vertebrates and invertebrates, intrinsic determinants are thought to act in neural progenitors to specify their identity and the identity of their neuronal progeny. However, the extent to which individual factors can contribute to this is poorly understood. We investigate the role of orthodenticle in the specification of an identified neuroblast (neuronal progenitor) lineage in the Drosophila brain. Loss of orthodenticle from this neuroblast affects molecular properties, neuroanatomical features, and functional inputs of progeny neurons, such that an entire central complex lineage transforms into a functional olfactory projection neuron lineage. This ability to change functional macrocircuitry of the brain through changes in gene expression in a single neuroblast reveals a surprising capacity for novel circuit formation in the brain and provides a paradigm for large-scale evolutionary modification of circuitry.

}, keywords = {Animals, Brain, Cell Lineage, Drosophila, Morphogenesis, Neurons}, issn = {2050-084X}, doi = {10.7554/eLife.04407}, author = {Sen, Sonia and Cao, Deshou and Choudhary, Ramveer and Biagini, Silvia and Wang, Jing W and Reichert, Heinrich and VijayRaghavan, K} } @article {519, title = {Unexpected histone H3 tail-clipping activity of glutamate dehydrogenase. (Mass spectrometry - Proteomics)}, journal = {J Biol Chem}, volume = {288}, year = {2013}, month = {2013 Jun 28}, pages = {18743-57}, abstract = {

Clipping of histone tails has been reported in several organisms. However, the significance and regulation of histone tail clipping largely remains unclear. According to recent discoveries H3 clipping has been found to be involved in regulation of gene expression and chromatin dynamics. Earlier we had provided evidence of tissue-specific proteolytic processing of histone H3 in White Leghorn chicken liver nuclei. In this study we identify a novel activity of glutamate dehydrogenase (GDH) as a histone H3-specific protease in chicken liver tissue. This protease activity is regulated by divalent ions and thiol-disulfide conversion in vitro. GDH specifically clips H3 in its free as well as chromatin-bound form. Furthermore, we have found an inhibitor that inhibits the H3-clipping activity of GDH. Like previously reported proteases, GDH too may have the potential to regulate/modulate post-translational modifications of histone H3 by removing the N-terminal residues of the histone. In short, our findings identify an unexpected proteolytic activity of GDH specific to histone H3 that is regulated by redox state, ionic concentrations, and a cellular inhibitor in vitro.

}, keywords = {Amino Acid Sequence, Animals, Binding Sites, Brain, Chickens, Chromatin, Cysteine Proteases, Disulfides, Epigenesis, Genetic, Gene Expression Regulation, Enzymologic, Glutamate Dehydrogenase, Histones, Hydrogen-Ion Concentration, Liver, Mass Spectrometry, Mice, Molecular Sequence Data, Rats, Recombinant Proteins, Salts, Sulfhydryl Compounds, Temperature}, issn = {1083-351X}, doi = {10.1074/jbc.M113.462531}, author = {Mandal, Papita and Verma, Naveen and Chauhan, Sakshi and Tomar, Raghuvir S} }