Complex regulation and multiple developmental functions of <Emphasis Type="Italic">misfire</Emphasis>, the <Emphasis Type="Italic">Drosophila melanogaster</Emphasis>ferlin gene

Background  

Ferlins are membrane proteins with multiple C2 domains and proposed functions in Ca²⁺ mediated membrane-membrane interactions in animals. Caenorhabditis elegans has two ferlin genes, one of which is required for sperm function. Mammals have several ferlin genes and mutations in the human dysferlin (DYSF) and otoferlin (OTOF) genes result in muscular dystrophy and hearing loss, respectively. Drosophila melanogaster has a single ferlin gene called misfire (mfr). A previous study showed that a mfr mutation caused male sterility because of defects in fertilization. Here we analyze the expression and structure of the mfr gene and the consequences of multiple mutations to better understand the developmental function of ferlins.     

Morphological and functional abnormalities in neuromuscular junctions of <Emphasis Type="Italic">Drosophila melanogaster</Emphasis> induced by human <Emphasis Type="Italic">APP</Emphasis> gene expression

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by a loss of neurocortical and hippocampal synapses that precedes amyloidosis and neurodegeneration and closely correlates with memory impairment. Mutations in the amyloid precursor protein (APP) cause familial AD and result in increased production of amyloid-β-protein (Aβ). To gain insight into the synaptic effects of APP protein in AD patients, wild-type APP, its mutant form APP-Swedish responsible for familial AD, and human beta-secretase gene were expressed in motor neurons of Drosophila melanogaster larvae. It was found that targeted expression of APP (APP-Swedish) in Drosophila larval motor neurons caused significant morphological and functional changes in neuromuscular junctions (NMJs)-a dramatic increase in the number of synaptic boutons and altered exocytosis revealed by incorporation of the styryl dye FM4-64. Analysis of the number and distribution of mitochondria showed that motor neurons overexpressing APP (APP-Swedish) had a significant reduction of functional mitochondria in the presynaptic terminal. Significant synaptic abnormalities were observed with APP (APP-Swedish) expression, as well as for double transgenes bearing APP (APP-Swedish) and human beta-secretase (BACE), which caused secretion of amyloid beta protein (Aβ). We suggest that APP participates in regulation of synaptic functions and its elevated expression leads to synaptic pathology independently from Aβ neurotoxic effects.     

Study of the enhancer-blocking activities of new boundaries in the <Emphasis Type="Italic">bithorax</Emphasis> complex of <Emphasis Type="Italic">Drosophila melanogaster</Emphasis>

It was shown earlier that the Mcp, Fab-7, and Fab-8 boundaries of the bithorax complex contain insulators that effectively block the enhancers of the yellow and white genes. Other boundaries have not been studied so far. The recent mapping of binding sites for the insulator protein dCTCF in the regulatory regions of the bithorax complex genes permitted the Fab-3, Fab-4, and Fab-6 boundaries to be localized. Here, we showed that, despite the presence of dCTCF-binding sites, fragments of the Fab-3, Fab-4, and Fab-6 boundaries do not exhibit the properties of insulators in the model system with the yellow and white genes. Moreover, in some regions of the genome the Fab-4 and Fab-6 boundaries display the properties of silencers.