<i>Drosophila</i> rab GDI mutants disrupt development but have normal rab membrane extraction

Ricard, Cynthia S.; Jakubowski, Janelle M.; Verbsky, John W.; Barbieri, M. Alejandro; Lewis, William M.; Fernández, G. Esteban; Vogel, Michael; Tsou, Christina; Prasad, Vinoy; Stahl, Philip D.; Waksman, Gabriel; Cheney, Clarissa M.

doi:10.1002/gene.10000

Cited by 15 publications

(7 citation statements)

References 50 publications

(70 reference statements)

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“…Four protein chaperones were identified, and the FKBP59 proline isomerase, which is active in the embryo, was detected as well (28). The GDP dissociation inhibitor is a factor important for intracellular protein transport (29). Another highly represented category functions in protein turnover.…”

Section: Resultsmentioning

confidence: 99%

Targets of microRNA regulation in the Drosophila oocyte proteome

Nakahara

Kim

Sciulli

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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MicroRNAs (miRNAs) are a class of small RNAs that silence gene expression. In animal cells, miRNAs bind to the 3 untranslated regions of specific mRNAs and inhibit their translation. Although some targets of a handful of miRNAs are known, the number and identities of mRNA targets in the genome are uncertain, as are the developmental functions of miRNA regulation. To identify the global range of miRNA-regulated genes during oocyte maturation of Drosophila, we compared the proteome from wild-type oocytes with the proteome from oocytes lacking the dicer-1 gene, which is essential for biogenesis of miRNAs. Most identified proteins appeared to be subject to translation inhibition. Their transcripts contained putative binding sites in the 3 untranslated region for a subset of miRNAs, based on computer modeling. The fraction of genes subject to direct and indirect repression by miRNAs during oocyte maturation appears to be small (4%), and the genes tend to share a common functional relationship in protein biogenesis and turnover. The preponderance of genes that control global protein abundance suggests this process is under tight control by miRNAs at the onset of fertilization.translation control S mall RNAs, including microRNAs (miRNAs) and short interfering RNAs, are components of a RNA-based mechanism of gene silencing (1, 2). The miRNA branch of RNA-based gene regulation is found in plants and animals (3, 4). miRNAs have a specific size of Ϸ22 nt, and they are processed from hairpin-loop RNA precursors by endoribonucleases of the Dicer class. These precursors are transcribed from genes within plant and animal genomes, with the number of miRNA genes found in different species roughly corresponding to 0.5-1% of the total number of genes in their genomes (5). Most miRNA genes are conserved between related species, and Ϸ30% of miRNA genes are highly conserved, with orthologs found in vertebrate and invertebrate genomes. This suggests that a significant fraction of miRNAs have evolutionarily conserved biological functions.miRNAs specifically repress gene expression by negatively regulating complementary mRNAs. Plant miRNAs generally cause degradation of complementary mRNAs by near-perfect basepairing (5). Conversely, most characterized miRNAs from animals repress gene expression by blocking the translation of complementary mRNAs into protein. They interact with their targets by imperfectly basepairing to mRNA sequences within the 3Ј UTR. The exact mechanism of translation inhibition is unknown, although miRNAs have been found not to interfere with translation initiation (5).A question of great interest concerns the functions of miRNAs in animals. Although the functions of only a few miRNAs are known, available evidence suggests that miRNAs play diverse and important roles in development. This conclusion is based on the mutant phenotypes of individual miRNA genes and on the identification of genes that are direct targets of miRNA regulation. In Caenorhabditis elegans, the genes lin-14, lin-28, lin-41, and hbl-1 are trans...

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Section: Resultsmentioning

confidence: 99%

Targets of microRNA regulation in the Drosophila oocyte proteome

Nakahara

Kim

Sciulli

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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“…To test whether rush and Gdi interact genetically, we analyzed the effect of rush mutation or overexpression in heterozygous Gdi AF160 loss-of-function mutants (Figure 9K; Ricard et al ., 2001). While loss of rush did not affect survival of heterozygous Gdi AF160 flies, Rush-GFP overexpression led to decreased viability of Gdi AF160 heterozygous mutants.…”

Section: Resultsmentioning

confidence: 99%

“…While the function of GDI in recycling of Rabs has been investigated in detail, not much is known about regulation of GDI itself (Cavalli et al ., 2001). A single GDI homologue exists in flies (Ricard et al ., 2001), but its function has not been well characterized.…”

Section: Introductionmentioning

confidence: 99%

The phosphoinositide-associated protein Rush hour regulates endosomal trafficking inDrosophila

Gailite

Egger-Adam

Wodarz

2012

MBoC

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The FYVE-domain protein Rush hour (Rush) binds directly to phosphatidylinositol 3-phosphate and to guanosine diphosphate dissociation inhibitor. It colocalizes with Rab7 and Hrs, and a rush null mutation interacts genetically with mutations in Rab5, Gdi, hrs, and carnation, the fly Vps33 homologue. Rush overexpression blocks the transition from late endosomes to lysosomes, pointing to a function for Rush in regulation of Rabs.

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“…Recent work on flotillin function in both plants and bacteria highlight a role in endocytosis. 46,47 Rab proteins are key components of the endocytic pathway and have a well-established role in coordinating development 48 and may provide an intersection between wound response localization and endocytosis. Future studies to determine the contribution of endocytic pathway components and their distinct localization patterns during epidermal wound response in the Drosophila embryo may provide further insight into cellular mechanism promoting wound repair.…”

Section: Discussion Of Findings and Relevant Literaturementioning

confidence: 99%

DrosophilaEmbryos as a Model for Wound-Induced Transcriptional Dynamics: Genetic Strategies to Achieve a Localized Wound Response

Juarez

2016

Advances in Wound Care

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While many studies have established a paradigm for tissue repair at the level of cellular remodeling, it is not clear how an organism restricts a response only to the injured region of a damaged tissue. Skin, the largest organ in the human body, is prone to injury, and repair of epidermal tissue represents a medically relevant system to investigate. Studies in provide a robust genetic system to identify molecular components that will positively impact repair and healing. The skin consists of a single-cell epidermal layer and relies on well-conserved cellular mechanisms to coordinate gene expression during development. Many studies have established that key developmental genes promote a response to epidermal injury, but the balance between activator and inhibitor signals to coordinate a localized response remains unknown. Discovery of a genetic pathway that promotes the restriction of transcriptional response to damage only in effected regions. Interestingly, genome-wide microarray studies have identified an intersection between gene expression after aseptic injury and activation of the innate immune response. The use of a transcriptional activation reporter provides an innovative approach to uncover well-conserved components that promote the localization of a response during epidermal injury and may influence other pathological conditions of tissue damage. The work reviewed in this critical review may lead to development of molecular strategies of repair and improved healing after injury or infection. The outcomes on the fundamental contribution of a transcriptional response to injury will be translatable to mammalian systems.

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Drosophila rab GDI mutants disrupt development but have normal rab membrane extraction

Cited by 15 publications

References 50 publications

Targets of microRNA regulation in the Drosophila oocyte proteome

Targets of microRNA regulation in the Drosophila oocyte proteome

The phosphoinositide-associated protein Rush hour regulates endosomal trafficking inDrosophila

DrosophilaEmbryos as a Model for Wound-Induced Transcriptional Dynamics: Genetic Strategies to Achieve a Localized Wound Response

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