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Alberto Ferrús

Publications and source records attributed to Alberto Ferrús.

9 recordsLinked to original sources
PubMed2006

Age-independent synaptogenesis by phosphoinositide 3 kinase.

Synapses are specialized communication points between neurons, and their number is a major determinant of cognitive abilities. These dynamic structures undergo developmental- and activity-dependent changes. During brain aging and certain diseases, synapses are gradually lost, causing mental decline. It is, thus, critical to identify the molecular mechanisms controlling synapse number. We show here that the levels of phosphoinositide 3 kinase (PI3K) regulate synapse number in both Drosophila larval motor neurons and adult brain projection neurons. The supernumerary synapses induced by PI3K overexpression are functional and elicit changes in behavior. Remarkably, PI3K activation induces synaptogenesis in aged adult neurons as well. We demonstrate that persistent PI3K activity is necessary for synapse maintenance. We also report that PI3K controls the expression and localization of synaptic markers in human neuroblastoma cells, suggesting that PI3K synaptogenic activity is conserved in humans. Thus, we propose that PI3K stimulation can be applied to prevent or delay synapse loss in normal aging and in neurological disorders.

Aging↗
PubMed2005

Tachykinin-related peptides modulate odor perception and locomotor activity in Drosophila.

The invertebrate tachykinin-related peptides (TKRPs) constitute a conserved family, structurally related to the mammalian tachykinins, including members such as substance P and neurokinins A and B. Although their expression has been documented in the brains of insects and mammals, their neural functions remain largely unknown, particularly in behavior. Here, we have studied the role of TKRPs in Drosophila. We have analyzed the olfactory perception and the locomotor activity of individuals in which TKRPs are eliminated in the nervous system specifically, by using RNAi constructs to silence gene expression. The perception of specific odorants and concentrations is modified towards a loss of sensitivity, thus resulting in a significant change of the behavioral response towards indifference. In locomotion assays, the TKRP-deficient flies show hyperactivity. We conclude that these peptides are modulators of olfactory perception and locomotion activity in agreement with their abundant expression in the olfactory lobes and central complex. In these brain centers, TKRPs seem to enhance the regulatory inhibition of the neurons in which they are expressed.

Animals↗
PubMed2004

Parkin and relatives: the RBR family of ubiquitin ligases.

Mutations in the parkin gene cause autosomal-recessive juvenile parkinsonism. Parkin encodes a ubiquitin-protein ligase characterized by having the RBR domain, composed of two RING fingers plus an IBR/DRIL domain. The RBR family is defined as the group of genes whose products contain an RBR domain. RBR family members exist in all eukaryotic species for which significant sequence data is available, including animals, plants, fungi, and several protists. The integration of comparative genomics with structural and functional data allows us to conclude that RBR proteins have multiple roles, not only in protein quality control mechanisms, but also as indirect regulators of transcription. A recently formulated hypothesis, based on a case of gene fusion, suggested that RBR proteins may be often part of cullin-containing ubiquitin ligase complexes. Recent data on Parkin protein agrees with that hypothesis. We discuss the involvement of RBR proteins in several neurodegenerative diseases and cancer.

Animals↗
PubMed2004

Transcription of Drosophila troponin I gene is regulated by two conserved, functionally identical, synergistic elements.

The Drosophila wings-up A gene encodes Troponin I. Two regions, located upstream of the transcription initiation site (upstream regulatory element) and in the first intron (intron regulatory element), regulate gene expression in specific developmental and muscle type domains. Based on LacZ reporter expression in transgenic lines, upstream regulatory element and intron regulatory element yield identical expression patterns. Both elements are required for full expression levels in vivo as indicated by quantitative reverse transcription-polymerase chain reaction assays. Three myocyte enhancer factor-2 binding sites have been functionally characterized in each regulatory element. Using exon specific probes, we show that transvection is based on transcriptional changes in the homologous chromosome and that Zeste and Suppressor of Zeste 3 gene products act as repressors for wings-up A. Critical regions for transvection and for Zeste effects are defined near the transcription initiation site. After in silico analysis in insects (Anopheles and Drosophila pseudoobscura) and vertebrates (Ratus and Coturnix), the regulatory organization of Drosophila seems to be conserved. Troponin I (TnI) is expressed before muscle progenitors begin to fuse, and sarcomere morphogenesis is affected by TnI depletion as Z discs fail to form, revealing a novel developmental role for the protein or its transcripts. Also, abnormal stoichiometry among TnI isoforms, rather than their absolute levels, seems to cause the functional muscle defects.

Animals↗
PubMed2003

Structural and functional changes in the olfactory pathway of adult Drosophila take place at a critical age.

The olfactory system of several holometabolous insect species undergoes anatomical changes after eclosion of the imago, following those occurring during metamorphosis. In parallel, odor experience and learning performance also evolve with age. Here, we analyze the case of adult Drosophila females. Synaptogenesis in the antennal lobe (AL) starts in late pupa and continues during the first days of adult life, at the same time as the behavioral response to odors matures. Individual olfactory glomeruli (DM6, DM2, and V) display specific growth patterns between days 1 and 12 of adult life. Experience can modify the olfactory pathway both structurally and functionally as shown by adaptation experiments. The modifications associated with this form of nonassociative learning seem to take place at a critical age. Exposure to benzaldehyde at days 2-5 of adult life, but not at 8-11, causes behavioral adaptation as well as structural changes in DM2 and V glomeruli. Altered levels in intracellular cAMP, caused by dunce and rutabaga mutants, do not affect the normal changes in glomerular size, at least at day 6 of development, but they prevent those elicited by experience, establishing a molecular difference between glomerular changes of intrinsic versus environmental origin. Taken together, these data demonstrate an imprinting-like phenomenon in the olfactory pathway of young Drosophila adults, and illustrate its glomerulus-specific dynamics.

Adaptation, Physiological↗
PubMed2003

Blocking sensory inputs to identified antennal glomeruli selectively modifies odorant perception in Drosophila.

Neural coding of sensory input is a major unsolved issue in neuroscience. Current experimental methods rely on neural activity recording or visualization following sensory stimulation. Most of them, however, do not include behavioral correlates on the actual perception by the animal. We present a novel approach to address olfaction and coding in adult Drosophila. Sensory input was selectively blocked in two subsets of sensory neurons that project to different, albeit overlapping, groups of central targets, by means of tetanus toxin expressed under the control of the yeast transcription factor Gal4. Glomeruli DL1, DL2, VM1, and VM4 were tested following stimulation with benzaldehyde, ethyl acetate, propionic acid, butanol, or acetone at various concentrations. The behavioral response was found to be modified in an odorant-specific and a concentration-dependent manner. Sensory input to DL2 and, to a minor extent, VM1 and/or VM4, appear to be required for benzaldehyde perception, while acetone is processed through DL1. None of these glomeruli, however, seem necessary for butanol perception. In addition, sexual differences were observed for some stimuli. These results demonstrate the behavioral relevance of odor representation as maps of glomerular activity generated in the antennal lobes following specific sensory input. The strategy used here should be useful to characterize olfactory coding, as new and selective Gal4 lines become available.

Animals↗
PubMed2002

Comparative genomics of the RBR family, including the Parkinson's disease-related gene parkin and the genes of the ariadne subfamily.

Genes of the RBR family are characterized by the RBR signature (two RING finger domains separated by an IBR/DRIL domain). The RBR family is widespread in eukaryotes, with numerous members in animals (mammals, Drosophila, Caenorhabditis) and plants (Arabidopsis). But yeasts, such as Saccharomyces cerevisiae or Schizosaccharomyces pombe, contain only two RBR genes. We determined the phylogenetic relationships and the most likely orthologs in different species of several family members for which functional data are available. These include: (1) parkin, whose mutations are involved in forms of familial Parkinson's disease; (2) the ariadne genes, recently characterized in Drosophila and mammals; (3) XYbp and Dorfin, two mammalian genes whose products interact with the centrosome; (4) XAP3, RBCK1, and UIP28, mammalian genes encoding Protein Kinase-C-binding proteins; and (5) ARA54, an androgen receptor coactivator. Because several of these genes are involved in ubiquitination, we used phylogenetic and structural analyses to explore the hypothesis that all RBR proteins might play a role in ubiquitination. We show that the involvement of RBR proteins in ubiquitination predates the animals-plants-fungi divergence. On the basis of the evidence provided by cases of gene fusion, we suggest that Ariadne proteins interact with cullin domain-containing proteins to form complexes with ubiquitin-ligase activity.

Animals↗
PubMedDate not supplied

Expression of enhancers is altered in Drosophila melanogaster hybrids.

The molecular foundations of evolution are difficult to trace because most protein sequences are virtually identical in closely related species. The largest fraction of sequence within the genome, however, is composed of noncoding sequences where regulatory elements locate to various sites. It has been suggested that changes in the activity of these elements may trigger evolutionary change. In Drosophila, the enhancer trap procedure identifies regulatory sequences in the genome after the insertion of a P-element-based construct. We generated new insertions and characterized their expression domains in the adult eye and larval imaginal disks using the white and LacZ reporter genes. Lines with robust expression patterns in D. melanogaster were analyzed in hybrids to test the conservation of regulatory mechanisms between species. Most of the enhancers used in this study modified their expression in hybrids with the mating species D. mauritiana and D. simulans. Expression changes resulted either in gain or loss of expression and were cell-type or hybrid-genome specific. Further characterization of a limited number of enhancers in D. melanogaster showed that expression domains could adapt to changes in cell number during development but not after the completion of cell proliferation. Also, expression of some enhancers appeared to be sensitive to heterochromatin from the Y but not the X chromosome. Taken together, these results demonstrate the high sensitivity of regulatory mechanisms of gene expression as a prime source of evolutionary change and suggest quantitative changes in available transcription factors as one of the mechanisms involved.

Animals↗