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Bieri, Tamberlyn; Blasiar, Darin; Ozersky, Philip; Antoshechkin, Igor; Bastiani, Carol; Canaran, Payan; Chan, Juancarlos; Chen, Nansheng; Chen, Wen J.; Davis, Paul A.; Fiedler, Tristan J.; Girard, Lisa; Han, Michael; Harris, Todd W.; Kishore, Ranjana; Lee, Raymond Y. N.; McKay, Sheldon; Müller, Hans‐Michael; Nakamura, Cecilia; Petcherski, Andrei; Rangarajan, Arun; Rogers, Anthony; Schindelman, Gary; Schwarz, Erich M.; Spooner, William; Tuli, Mary Ann; Auken, Kimberly Van; Wang, Daniel; Wang, Xiaodong; Williams, Gary W.; Durbin, Richard; Stein, Lincoln; Sternberg, Paul W.; Strouboulis, John

doi:10.1093/nar/gkl818

Cited by 81 publications

(79 citation statements)

References 13 publications

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“…Functional data were obtained from SymAtlas (http:// symatlas.gnf.org/SymAtlas/; Su et al 2002Su et al , 2004 Bieri et al 2007) for Caenorhabditis elegans genes. For human RBR genes, the microarray data in SymAtlas (datasets GNF1H.gcRMA and GNF1H.MAS5, each one with 79 independent results for different tissues or cell types) were downloaded.…”

Section: Methodsmentioning

confidence: 99%

RBR Ubiquitin Ligases: Diversification and Streamlining in Animal Lineages

Marı́n

2009

J Mol Evol

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The patterns of emergence and disappearance in animal species of genes encoding RBR ubiquitin ligases are described. RBR genes can be classified into subfamilies (Parkin, Ariadne, Dorfin, ARA54, etc.) according to sequence and structural data. Here, I show that most animal-specific RBR subfamilies emerged early in animal evolution, and that ancient animals, before the cnidarian/ bilaterian split, had a set of RBR genes, which was as complex as the one currently found in mammals. However, some lineages (nematodes, dipteran insects) have recently suffered multiple losses, leading to a highly simplified set of RBR genes. Genes of a particular RBR subfamily, characterized by containing a helicase domain and so far found only in plants, are present also in some animal species. The meaning of these patterns of diversification and streamlining are discussed at the light of functional data. Extreme evolutionary conservation may be related to gene products having housekeeping functions.

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Section: Methodsmentioning

confidence: 99%

RBR Ubiquitin Ligases: Diversification and Streamlining in Animal Lineages

Marı́n

2009

J Mol Evol

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“…Mammalian and yeast Rab5 GTP exchange factors (GEFs), which promote cycling of GTPases from the GDP to GTPbound conformation, all share a canonical Vps9 domain 40 . There are three Vps9-domain containing proteins in the nematode, rme-6, rabx-5, and tag-333 41 . RME-6 and RABX-5 are both homologues of mammalian RabEx-5 and are required for generation of RAB-5(+) endosomes in coelomocytes 42 and in the somatic sheath cells (Supplementary Figure S1).…”

Section: Rab-5 and Rab-7 Are Required For Efficient Phagosome Maturationmentioning

confidence: 99%

“…Therefore, we focused on the 14 FYVE-domain containing proteins and 12 PX-domain containing proteins in the nematode genome 41 . Analysis of worms with disruptions in the 14 FYVE domain-containing proteins (either existing mutants in seven genes, or RNAi-mediated knockdown of the other seven candidates) showed no obvious defect in corpse removal in the germ line.…”

Section: Rab-5 and Rab-7 Are Required For Efficient Phagosome Maturationmentioning

confidence: 99%

“…Following elimination of all genes previously shown to cause developmental delay or sterility 41 , we identified 61 genes whose knockdown reproducibly resulted in decreased AO staining (Figure 3e , Supplementary Table S1). In addition to the known genes required for corpse recognition (ced-1) and internalization (ced-5 and ced-6) present in the RNAi library 50 , we also identified components of the Arp2/3 complex in C. elegans, arx-3 and arx-5 51 .…”

Section: An Unbiased Genetic Screen Identifies Additional Genes Requimentioning

confidence: 99%

“…Additionally, we identified wip-1 and C24A1.3 (a tyrosine kinase), which may regulate activity of the small GTPase Cdc42 during corpse removal. Among the remaining genes, homologues of several candidates, phi-25, dyci-1, rab-10, and rme-8, suggest these genes may play a role during corpse processing and phagosome maturation 41 . Further, we isolated vha-15, a vacuolar ATPase, which may be required for acidification of the lysosome and hence onset of AO staining.…”

Section: An Unbiased Genetic Screen Identifies Additional Genes Requimentioning

confidence: 99%

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A pathway for phagosome maturation during engulfment of apoptotic cells

et al. 2008

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The efficient removal of apoptotic cells is critical for the physiological well-being of the organism 1 Ã 4 ; defects in corpse removal have been linked to autoimmune disease 4,5 . While several players regulating the early steps of corpse recognition and internalization have been characterized 6 , the molecules and mechanisms relevant to the subsequent processing of the internalized corpses are poorly understood. Here, we identify a novel pathway for the processing of internalized apoptotic cells in C. elegans and in mammals. First, we show that RAB-5 and RAB-7 are sequentially recruited to phagosomes containing apoptotic corpses as they mature within phagocytes, and that both proteins are required for efficient corpse clearance. We then used targeted genetic screens to identify players regulating the recruitment and/or retention of Rab5 and Rab7 to phagosomes. Seven members of the HOPS complex (a Rab7 activator/effector complex) were required for Rab7 localization or retention on phagosomes. In an effort to identify factors that regulate Rab5 recruitment, we undertook an unbiased reverse genetic screen and identified 61 genes potentially required for corpse removal. In-depth analysis of two candidate genes, vps-34 and dyn-1/ dynamin, showed accumulation of internalized, but undegraded corpses within abnormal phagosomes that are defective in RAB-5 recruitment. Using a series of genetic and biochemical experiments in worms and mammalian cells, we ordered these proteins in a pathway, with DYN-1 functioning upstream of VPS-34, in the recruitment/retention of Rab5 to the nascent phagosome. Further, we identified a novel biochemical complex containing Vps34, dynamin and Rab5 GDP , providing a mechanism for Rab5 recruitment to the nascent phagosome.Removal of apoptotic cells (engulfment) is an essential process that occurs throughout life in multi-cellular animals as part of development, homeostasis, and wound healing1Ã4 , 7 , 8. Engulfment) can be broken down into a series of steps, comprising recognition, internalization, phagosome maturation and finally lysosomal degradation of the apoptotic cell by the phagocyte. In mammals, impaired clearance of apoptotic cell corpses can lead to exposure of autoantigens, resulting in onset of autoimmune diseases, such as systemic lupus erythematosus 4,9,10 . Modulation of the engulfment process is therefore a potential therapeutic target in these conditions. One of the fundamental challenges in understanding how defects in engulfment of apoptotic cells translates into diseased states is the identification of critical players involved in corpse removal and how these proteins orchestrate the different stages of engulfment.The nematode C. elegans represents a powerful genetic tool for the study of programmed cell death 11,12 . Large numbers of cells are induced to die during two periods in the life of a worm: during embryonic and larval morphogenesis and during germ cell development 13 . Genetic studies have identified two evolutionarily conserved signaling pathways invol...

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Identification of a CREB‐dependent serotonergic pathway and neuronal circuit regulating foraging behavior in Caenorhabditis elegans: A useful model for mental disorders and their treatments?

Zubenko

Jones

Estevez

et al. 2008

American J of Med Genetics Pt B

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The cAMP-response element binding protein (CREB)-mediated cell signaling pathway is conserved through evolution and participates in a broad range of complex behaviors of divergent species including man. This study describes the integration of genetic, pharmacologic, and anatomic methods to elucidate a serotonergic signaling pathway by which the CREB homolog CRH-1 controls foraging rate (FR) in the model organism C. elegans, along with the complete neuronal circuit through which this pathway operates. In the anterior afferent arm of the circuit, CRH-1 controls FR by regulating the expression of tph-1, the sole structural gene for tryptophan hydroxylase, in serotonergic sensory (ADF) neurons whose post-synaptic effects are mediated through 5HT2-like SER-1 receptors. The posterior afferent limb of the circuit includes an interneuron (RIH) that does not express tph-1 and whose serotonergic phenotype is dependent on the contribution of this neurotransmitter from another source, probably the ADF neurons. The postsynaptic effects of the RIH interneuron are mediated through 5HT1-like SER-4 receptors. This model has potential utility for the study of clinical disorders and experimental therapeutics. Furthermore, the discovery of serotonergic neurons that depend on other sources for their neurotransmitter phenotype could provide a mechanism for rapidly altering the number and distribution of serotonergic pathways in developing and adult nervous systems, providing a dimension of functional complexity that has been previously unrecognized.

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WormBase: new content and better access

Cited by 81 publications

References 13 publications

RBR Ubiquitin Ligases: Diversification and Streamlining in Animal Lineages

RBR Ubiquitin Ligases: Diversification and Streamlining in Animal Lineages

A pathway for phagosome maturation during engulfment of apoptotic cells

Identification of a CREB‐dependent serotonergic pathway and neuronal circuit regulating foraging behavior in Caenorhabditis elegans: A useful model for mental disorders and their treatments?

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