What's new in edition 47 part 4/5 September 2006 updates for genes N-R

Updates at previously included gene sites:

genes N-R listed below

Nanos Netrin-A and Netrin-B Neuroglian Odorant receptor 83b Oskar

PAR-domain protein 1 Phosphotidylinositol 3 kinase 92E Rho1 Rolled/MAP kinase Roughest

What's new in edition 47:
part 1/5 new genes | updates: part 2/5 genes A-E | part 3/5 genes F-M | part 5/5 genes S-Z

Nanos: Glorund, a Drosophila hnRNP F/H homolog, is an ovarian repressor of nanos translation

Patterning of the anterior-posterior body axis of the Drosophila embryo requires production of Nanos protein selectively in the posterior. Spatially restricted Nanos synthesis is accomplished by translational repression of unlocalized nanos mRNA together with translational activation of posteriorly localized nanos. Repression of unlocalized nanos mRNA is mediated by a bipartite translational control element (TCE) in its 3' untranslated region. TCE stem-loop II functions during embryogenesis, through its interaction with the Smaug repressor. Stem-loop III represses unlocalized nanos mRNA during oogenesis, but trans-acting factors that carry out this function have remained elusive. This study identifies a Drosophila hnRNP, Glorund, that interacts specifically with stem-loop III. The ability of the TCE to repress translation in vivo reflects its ability to bind Glorund in vitro. These data, together with the analysis of a glorund null mutant, reveal a specific role for an hnRNP in repression of nanos translation during oogenesis (Kalifa, 2006).

Netrin-A and Netrin-B: Netrins guide Drosophila commissural axons at short range

Netrins are secreted axon guidance molecules required for commissure formation in a wide range of animal species, including C. elegans, Drosophila melanogaster and mice. They are generally thought to function as chemoattractants, acting at a distance to direct commissural axon growth toward the midline of the central nervous system. This study shows, however, that D. melanogaster commissural axons still orient normally and reach the midline even in the complete absence of netrins, though some of them fail to cross the midline. Tethering endogenous netrin to the membrane selectively disrupts its long-range but not short-range activity, yet still allows normal commissure formation. It is therefore proposed that netrins act in commissural axon guidance as short-range cues that promote midline crossing, not as long-range chemoattractants (Brankatschk, 2006).

Neuroglian: Effects of Mutation

Drosophila Neuroglian (Nrg) and its vertebrate homolog L1-CAM are cell-adhesion molecules (CAM) that have been well studied in early developmental processes. Mutations in the human gene result in a broad spectrum of phenotypes (the CRASH-syndrome) that include devastating neurological disorders such as spasticity and mental retardation. Although the role of L1-CAMs in neurite extension and axon pathfinding has been extensively studied, much less is known about their role in synapse formation. A single extracellular missense mutation in nrg⁸⁴⁹ mutants disrupts the physiological function of a central synapse in Drosophila. The identified giant neuron in nrg⁸⁴⁹ mutants make a synaptic terminal on the appropriate target, but ultrastructural analysis reveals in the synaptic terminal a dramatic microtubule reduction, which is likely to be the cause for disrupted active zones. The results reveal that tyrosine phosphorylation of the intracellular ankyrin binding motif is reduced in mutants, and cell-autonomous rescue experiments demonstrate the indispensability of this tyrosine in giant-synapse formation. This function in giant-synapse formation is conserved in human L1-CAM but not in either human L1-CAM with a pathological missense mutation or in two isoforms of the paralogs NrCAM and Neurofascin. It is concluded that Nrg has a function in synapse formation by organizing microtubules in the synaptic terminal. This novel synaptic function is conserved in human L1-CAM but is not common to all L1-type proteins. Finally, the findings suggest that some aspects of L1-CAM-related neurological disorders in humans may result from a disruption in synapse formation rather than in axon pathfinding (Godenschwege, 2006).

Odorant receptor 83b: Protein interactions

Drosophila olfactory sensory neurons (OSNs) each express two odorant receptors (ORs): a divergent member of the OR family and the highly conserved, broadly expressed receptor OR83b. OR83b is essential for olfaction in vivo and enhances OR function in vitro, but the molecular mechanism by which it acts is unknown. This study demonstrates that OR83b heterodimerizes with conventional ORs early in the endomembrane system in OSNs, couples these complexes to the conserved ciliary trafficking pathway, and is essential to maintain the OR/OR83b complex within the sensory cilia, where odor signal transduction occurs. The OR/OR83b complex is necessary and sufficient to promote functional reconstitution of odor-evoked signaling in sensory neurons that normally respond only to carbon dioxide. Unexpectedly, unlike all known vertebrate and nematode chemosensory receptors, Drosophila ORs and OR83b adopt a novel membrane topology with their N-termini and the most conserved loops in the cytoplasm. These loops mediate direct association of ORs with OR83b. These results reveal that OR83b is a universal and integral part of the functional OR in Drosophila. This atypical heteromeric and topological design appears to be an insect-specific solution for odor recognition, making the OR/OR83b complex an attractive target for the development of highly selective insect repellents to disrupt olfactory-mediated host-seeking behaviors of insect disease vectors (Benton, 2006).

Oskar: Bruno acts as a dual repressor of oskar translation, promoting mRNA oligomerization and formation of silencing particles

Prior to reaching the posterior pole of the Drosophila oocyte, oskar mRNA is translationally silenced by Bruno binding to BREs in the 3' untranslated region. The eIF4E binding protein Cup interacts with Bruno and inhibits oskar translation. Validating current models, the mechanism proposed for Cup-mediated repression has been directly demonstrated: inhibition of small ribosomal subunit recruitment to oskar mRNA. However, 43S complex recruitment remains inhibited in the absence of functional Cup, uncovering a second Bruno-dependent silencing mechanism. This mechanism involves mRNA oligomerization and formation of large (50S-80S) silencing particles that cannot be accessed by ribosomes. Bruno-dependent mRNA oligomerization into silencing particles emerges as a mode of translational control that may be particularly suited to coupling with mRNA transport (Chekulaeva, 2006).

PAR-domain protein 1: Pdp1 is a regulator of larval growth, mitosis and endoreplication

PDP1 is a basic leucine zipper (bZip) transcription factor that is expressed at high levels in the muscle, epidermis, gut and fat body of the developing Drosophila embryo. Three mutant alleles of Pdp1 have been identified, each having a similar phenotype. This study describes in detail the Pdp1 mutant allele, Pdp1^p205, which is null for both Pdp1 RNA and protein. Interestingly, homozygous Pdp1^p205 embryos develop normally, hatch and become viable larvae. Analyses of Pdp1 null mutant embryos reveal that the overall muscle pattern is normal as is the patterning of the gut and fat body. Pdp1^p205 larvae also appear to have normal muscle and gut function and respond to ecdysone. These larvae, however, are severely growth delayed and arrested. Furthermore, although Pdp1 null larvae live a normal life span, they do not form pupae and thus do not give rise to eclosed flies. The stunted growth of Pdp1^p205 larvae is accompanied by defects in mitosis and endoreplication similar to that associated with nutritional deprivation. The cellular defects resulting from the Pdp1^p205 mutation are not cell autonomous. Moreover, PDP1 expression is sensitive to nutritional conditions, suggesting a link between nutrition, PDP1 isotype expression and growth. These results indicate that Pdp1 has a critical role in coordinating growth and DNA replication (Reddy, 2006).

Phosphotidylinositol 3 kinase 92E: FOXO-independent suppression of programmed cell death by the PI3K/Akt signaling pathway in Drosophila

Signaling through the PI3K/Akt/FOXO pathway plays an important role in vertebrates in protecting cells from programmed cell death. PI3K and Akt have been similarly shown to be involved in survival signaling in Drosophila. However, it is not known whether PI3K and Akt execute this function by controlling a pro-apoptotic activity of Drosophila FOXO. This study shows that elevated signaling through PI3K and Akt can prevent developmentally controlled death in the salivary glands of the fruit fly. Drosophila FOXO is not required for normal salivary gland death and the rescue of salivary gland death by PI3K occurs independent of FOXO. These results give support to the notion that FOXOs have acquired pro-apoptotic functions after separation of the vertebrate and invertebrate lineages (Liu, 2006).

Rho1: Coordination of microtubule and microfilament dynamics by Drosophila Rho1, Spire and Cappuccino

The actin-nucleation factors Spire and Cappuccino (Capu) regulate the onset of ooplasmic streaming in Drosophila melanogaster. Although this streaming event is microtubule-based, actin assembly is required for its timing. It is not understood how the interaction of microtubules and microfilaments is mediated in this context. This study demonstrates that Capu and Spire have microtubule and microfilament crosslinking activity. The spire locus encodes several distinct protein isoforms (SpireA, SpireC and SpireD). SpireD nucleates actin, but the activity of the other isoforms has not been addressed. This study finds that SpireD does not have crosslinking activity, whereas SpireC is a potent crosslinker. SpireD binds to Capu and inhibits F-actin/microtubule crosslinking, and activated Rho1 abolishes this inhibition, establishing a mechanistic basis for the regulation of Capu and Spire activity. It is proposed that Rho1, Cappuccino and Spire are elements of a conserved developmental cassette that is capable of directly mediating crosstalk between microtubules and microfilaments (Rosales-Nieves, 2006).

Rolled/MAP kinase: MAP kinase subcellular localization controls both pattern and proliferation in the developing Drosophila wing

Mitogen-activated protein kinases (MAPKs) phosphorylate target proteins in both the cytoplasm and nucleus, and a strong correlation exists between the subcellular localization of MAPK and resulting cellular responses. It was thought that MAPK phosphorylation was always followed by rapid nuclear translocation. However, MAPK phosphorylation is not always sufficient for nuclear translocation in vivo. In the developing Drosophila wing, MAPK-mediated signaling is required both for patterning and for cell proliferation, although the mechanism of this differential control is not fully understood. This study shows that phosphorylated MAPK (pMAPK) is held in the cytoplasm in differentiating larval and pupal wing vein cells, and this cytoplasmic hold is required for vein cell fate. At the same time, MAPK does move into the nucleus of other wing cells where it promotes cell proliferation. A novel Ras pathway bifurcation is proposed in Drosophila and the results suggest a mechanism by which MAPK phosphorylation can signal two different cellular outcomes (differentiation versus proliferation) based on the subcellular localization of MAPK (Marenda, 2006).

Roughest: The adaptor protein X11Lalpha/Dmint1 interacts with the PDZ-binding domain of the cell recognition protein Rst in Drosophila

The Drosophila cell adhesion molecule Roughest (Rst) plays key roles during the development of the embryonic musculature, spacing of ommatidia in the compound eye and of sensory organs on the antenna, as well as in the neuronal wiring of the optic lobe. In rst^CT mutants lacking the cytoplasmic domain of the Rst protein, cell sorting and apoptosis in the eye are affected, suggesting a requirement of this domain for Rst function. To identify potential interacting proteins, yeast two-hybrid screens were performed using as baits the cytoplasmic domains of Rst and its paralogue Kirre. Among several putative interactors, two paralogous Drosophila PDZ motif proteins related to X11/Mint were identified. X11/Mint family members in C. elegans (LIN-10) and vertebrates are believed to function as adaptor proteins and to regulate the assembly of multi-subunit complexes at the synapse, thereby linking the vesicle cycle to cell adhesion. Using genetic, cell biological, and biochemical approaches, the interaction of Rst with X11La has been shown to be of biological significance. The proteins interact, for example, in the context of cell sorting in the pupal retina (Vishnu, 2006).

What's new in edition 47 of the Interactive Fly:

part 1/5 new genes | part 2/5 genes A-E | part 3/5 genes F-M | part 5/5 genes S-Z

Home page: The Interactive Fly © 1995, 1996 Thomas B. Brody, Ph.D.