RESUMO
Aggression is known to be regulated by pheromonal information in many species. But how central brain neurons processing this information modulate aggression is poorly understood. Using the fruit fly model of Drosophila melanogaster, we systematically characterize the role of a group of sexually dimorphic GABAergic central brain neurons, popularly known as mAL, in aggression regulation. The mAL neurons are known to be activated by male and female pheromones. In this report, we show that mAL activation robustly increases aggression, whereas its inactivation decreases aggression and increases intermale courtship, a behavior considered reciprocal to aggression. GABA neurotransmission from mAL is crucial for this behavior regulation. Exploiting the genetic toolkit of the fruit fly model, we also find a small group of approximately three to five GABA+ central brain neurons with anatomical similarities to mAL. Activation of the mAL resembling group of neurons is necessary for increasing intermale aggression. Overall, our findings demonstrate how changes in activity of GABA+ central brain neurons processing pheromonal information, such as mAL in Drosophila melanogaster, directly modulate the social behavior of aggression in male-male pairings.
Assuntos
Agressão/fisiologia , Comportamento Animal/fisiologia , Encéfalo/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Interneurônios/metabolismo , Ácido gama-Aminobutírico/metabolismo , Animais , Corte , Masculino , Neurônios/metabolismo , Feromônios/metabolismo , Comportamento Sexual Animal/fisiologia , Comportamento SocialRESUMO
A model has been proposed in which JIL-1 kinase-mediated H3S10 and H2Av phosphorylation is required for transcriptional elongation and heat shock-induced chromatin decondensation. However, here we show that although H3S10 phosphorylation is indeed compromised in the H2Av null mutant, chromatin decondensation at heat shock loci is unaffected in the absence of JIL-1 as well as of H2Av and that there is no discernable decrease in the elongating form of RNA polymerase II in either mutant. Furthermore, mRNA for the major heat shock protein Hsp70 is transcribed at robust levels in both H2Av and JIL-1 null mutants. Using a different chromatin remodeling paradigm that is JIL-1 dependent, we provide evidence that ectopic tethering of JIL-1 and subsequent H3S10 phosphorylation recruits PARP-1 to the remodeling site independently of H2Av phosphorylation. These data strongly suggest that H2Av or H3S10 phosphorylation by JIL-1 is not required for chromatin decondensation or transcriptional elongation in Drosophila.
Assuntos
Cromatina/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Histonas/metabolismo , Fosfosserina/metabolismo , Elongação da Transcrição Genética , Animais , Eucromatina/metabolismo , Proteínas de Fluorescência Verde/metabolismo , Resposta ao Choque Térmico/genética , Immunoblotting , Imuno-Histoquímica , Óperon Lac/genética , Mutação/genética , Fosforilação , Poli(ADP-Ribose) Polimerases/metabolismo , Cromossomos Politênicos/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , TransgenesRESUMO
Crustaceans played a major role in establishing that gamma-aminobutyric acid (GABA) functioned as an inhibitory transmitter compound. In fact, it is now widely accepted that GABA is the major inhibitory transmitter compound in all animal species where it has been examined. The story of its acceptance as a neurotransmitter, however, is more interesting than that. GABA was first isolated from mammalian brains by three laboratories in 1950. Great excitement surrounded this discovery, and many laboratories began exploring its function. This excitement peaked at two large international congresses in the United States at the end of the first decade of study, where a consensus of major figures in the field was that GABA was not a transmitter compound. How could this have happened?
RESUMO
Aggression is an intrinsic trait that organisms of almost all species, humans included, use to get access to food, shelter, and mating partners. To maximize fitness in the wild, an organism must vary the intensity of aggression toward the same or different stimuli. How much of this variation is genetic and how much is externally induced, is largely unknown but is likely to be a combination of both. Irrespective of the source, one of the principal physiological mechanisms altering the aggression intensity involves neuromodulation. Any change or variation in aggression intensity is most likely governed by a complex interaction of several neuromodulators acting via a meshwork of neural circuits. Resolving aggression-specific neural circuits in a mammalian model has proven challenging due to the highly complex nature of the mammalian brain. In that regard, the fruit fly model Drosophila melanogaster has provided insights into the circuit-driven mechanisms of aggression regulation and its underlying neuromodulatory basis. Despite morphological dissimilarities, the fly brain shares striking similarities with the mammalian brain in genes, neuromodulatory systems, and circuit-organization, making the findings from the fly model extremely valuable for understanding the fundamental circuit logic of human aggression. This review discusses our current understanding of how neuromodulators regulate aggression based on findings from the fruit fly model. We specifically focus on the roles of Serotonin (5-HT), Dopamine (DA), Octopamine (OA), Acetylcholine (ACTH), Sex Peptides (SP), Tachykinin (TK), Neuropeptide F (NPF), and Drosulfakinin (Dsk) in fruit fly male and female aggression.
RESUMO
In this study we provide evidence that the spindle matrix protein Skeletor in Drosophila interacts with the human ASCIZ (also known as ATMIN and ZNF822) ortholog, Digitor/dASCIZ. This interaction was first detected in a yeast two-hybrid screen and subsequently confirmed by pull-down assays. We also confirm a previously documented function of Digitor/dASCIZ as a regulator of Dynein light chain/Cut up expression. Using transgenic expression of a mCitrine-labeled Digitor construct, we show that Digitor/dASCIZ is a nuclear protein that is localized to interband and developmental puff chromosomal regions during interphase but redistributes to the spindle region during mitosis. Its mitotic localization and physical interaction with Skeletor suggest the possibility that Digitor/dASCIZ plays a direct role in mitotic progression as a member of the spindle matrix complex. Furthermore, we have characterized a P-element insertion that is likely to be a true null Digitor/dASCIZ allele resulting in complete pupal lethality when homozygous, indicating that Digitor/dASCIZ is an essential gene. Phenotypic analysis of the mutant provided evidence that Digitor/dASCIZ plays critical roles in regulation of metamorphosis and organogenesis as well as in the DNA damage response. In the Digitor/dASCIZ null mutant larvae there was greatly elevated levels of γH2Av, indicating accumulation of DNA double-strand breaks. Furthermore, reduced levels of Digitor/dASCIZ decreased the resistance to paraquat-induced oxidative stress resulting in increased mortality in a stress test paradigm. We show that an early developmental consequence of the absence of Digitor/dASCIZ is reduced third instar larval brain size although overall larval development appeared otherwise normal at this stage. While Digitor/dASCIZ mutant larvae initiate pupation, all mutant pupae failed to eclose and exhibited various defects in metamorphosis such as impaired differentiation, incomplete disc eversion, and faulty apoptosis. Altogether we provide evidence that Digitor/dASCIZ is a nuclear protein that performs multiple roles in Drosophila larval and pupal development.
Assuntos
Proteínas Cromossômicas não Histona/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila/metabolismo , Proteínas Associadas à Matriz Nuclear/metabolismo , Fatores de Transcrição/metabolismo , Animais , Núcleo Celular/metabolismo , Proteínas Cromossômicas não Histona/química , Proteínas Cromossômicas não Histona/genética , Dano ao DNA , Drosophila/crescimento & desenvolvimento , Proteínas de Drosophila/química , Proteínas de Drosophila/genética , Drosophila melanogaster/embriologia , Drosophila melanogaster/metabolismo , Expressão Gênica , Genótipo , Resposta ao Choque Térmico , Humanos , Interfase , Metamorfose Biológica , Mitose , Mutação , Proteínas Associadas à Matriz Nuclear/química , Proteínas Associadas à Matriz Nuclear/genética , Ligação Proteica , Domínios e Motivos de Interação entre Proteínas , Transporte Proteico , Transdução de Sinais , Estresse Fisiológico , Fatores de Transcrição/química , Transcrição GênicaRESUMO
The chromodomain protein, Chromator, is localized to chromosomes during interphase; however, during cell division together with other nuclear proteins Chromator redistributes to form a macro molecular spindle matrix complex that embeds the microtubule spindle apparatus. It has been demonstrated that the CTD of Chromator is sufficient for localization to the spindle matrix and that expression of this domain alone could partially rescue Chro mutant microtubule spindle defects. Furthermore, the presence of frayed and unstable microtubule spindles during mitosis after Chromator RNAi depletion in S2 cells indicated that Chromator may interact with microtubules. In this study using a variety of biochemical assays we have tested this hypothesis and show that Chromator not only has binding activity to microtubules with a Kd of 0.23 µM but also to free tubulin. Furthermore, we have mapped the interaction with microtubules to a relatively small stretch of 139 amino acids in the carboxy-terminal region of Chromator. This sequence is likely to contain a novel microtubule binding interface since database searches did not find any sequence matches with known microtubule binding motifs.