Richie CT et al. (2011) J Cell Sci "Protein phosphatase 5 is a negative regulator of separase function during cortical granule exocytosis in C. elegans."

Furuta T, Chestnut B, Schumacher JM, Golden A, Bembenek JN, Richie CT, Wallenfang M

[J Cell Sci, 2011]

Mutations in the Caenorhabditis elegans separase gene, sep-1, are embryonic lethal. Newly fertilized mutant embryos have defects in polar body extrusion, fail to undergo cortical granule exocytosis, and subsequently fail to complete cytokinesis. Chromosome nondisjunction during the meiotic divisions is readily apparent after depletion of sep-1 by RNAi treatment, but much less so in hypomorphic mutant embryos. To identify factors that influence the activity of separase in cortical granule exocytosis and cytokinesis, we carried out a genetic suppressor screen. A mutation in the protein phosphatase 5 (pph-5) gene was identified as an extragenic suppressor of sep-1. This mutation suppressed the phenotypes of hypomorphic separase mutants but not RNAi depleted animals. Depletion of pph-5 caused no phenotypes on its own, but was effective in restoring localization of mutant separase to vesicles and suppressing cortical granule exocytosis and cytokinesis phenotypes. The identification of PPH-5 as a suppressor of separase suggests that a new phospho-regulatory pathway plays an important role in regulating anaphase functions of separase.

Wilson LD et al. (2011) BMC Dev Biol "Fertilization in C. elegans requires an intact C-terminal RING finger in sperm protein SPE-42."

Mieczkowski BD, Kroft TL, Thoemke K, Rumbley JN, Richie AL, Wilson LD, Sackett JM

[BMC Dev Biol, 2011]

BACKGROUND: The C. elegans sperm protein SPE-42, a membrane protein of unknown structure and molecular function, is required for fertilization. Sperm from worms with spe-42 mutations appear normal but are unable to fertilize eggs. Sequence analysis revealed the presence of 8 conserved cysteine residues in the C-terminal cytoplasmic domain of this protein suggesting these residues form a zinc-coordinating RING finger structure. RESULTS: We made an in silico structural model of the SPE-42 RING finger domain based on primary sequence analysis and previously reported RING structures. To test the model, we created spe-42 transgenes coding for mutations in each of the 8 cysteine residues predicted to coordinate Zn++ ions in the RING finger motif. Transgenes were crossed into a spe-42 null background and protein function was measured by counting progeny. We found that all 8 cysteines are required for protein function. We also showed that sequence differences between the C-terminal 29 and 30 amino acids in C. elegans and C. briggsae SPE-42 following the RING finger domain are not responsible for the failure of the C. briggsae SPE-42 homolog to rescue C. elegans spe-42 mutants. CONCLUSIONS: The results suggest that a bona fide RING domain is present at the C-terminus of the SPE-42 protein and that this motif is required for sperm-egg interactions during C. elegans fertilization. Our structural model of the RING domain provides a starting point for further structure-function analysis of this critical region of the protein. The C-terminal domain swap experiment suggests that the incompatibility between the C. elegans and C. briggsae SPE-42 proteins is caused by small amino acid differences outside the C-terminal domain.

Wilson LD et al. (2018) Mol Reprod Dev "The C. elegans spe-49 gene is required for fertilization and encodes a sperm-Specific transmembrane protein homologous to SPE-42."

Hall RW, Richie AL, Rumbley JN, Mieczkowski BD, Wilson LD, Obakpolor OA, Kroft TL, Jones AM, Fall GT

[Mol Reprod Dev, 2018]

Fertilization, the fusion of sperm and oocyte to form a zygote, is the first and arguably the most important cell-cell interaction event in an organism's life. Forward and reverse genetic approaches in the nematode Caenorhabditis elegans have identified many genes that are required for gametogenesis and fertilization, and thus are beginning to elucidate the molecular pathways that underlie these processes. We identified an allele of the spe-49 gene in an F2 mutagenesis screen for spermatogenesis defective (spe) mutants. Worms mutant for spe-49 produce sperm that have normal morphology, activate to form amoeboid spermatozoa, and can migrate to and maintain their position in the hermaphrodite reproductive tract but fail to fertilize oocytes. This phenotype puts spe-49 in the spe-9 class of late-acting genes that function in sperm at the time of fertilization. We cloned the spe-49 gene through a combination of deficiency mapping, transgenic rescue, and genomic sequencing. spe-49 mRNA is enriched in male germ cells, and the cDNA encodes a predicted 772 amino acid six-pass transmembrane protein that is homologous to SPE-42. Indeed, SPE-49 and SPE-42 have identical predicted membrane topology and domain structure including a large extracellular domain with six conserved cysteine residues, a DC-STAMP domain, and a C-terminal cytoplasmic domain containing a C4-C4 RING finger motif. The presence of two SPE-42 homologs in animal genomes from worms to humans suggests that these proteins are highly conserved components of the molecular apparatus required for sperm-oocyte recognition, binding, and fusion. This article is protected by copyright. All rights reserved.

Kazatskaya, Anna et al. (2020) MicroPubl Biol

de Bono, Mario, Amin-Wetzel, Niko, Sengupta, Piali, Philbrook, Alison, Kazatskaya, Anna, Yuan, Lisa

[MicroPubl Biol, 2020]

A subset of sensory neurons in C. elegans contains compartmentalized sensory structures termed cilia at their distal dendritic ends (Ward et al. 1975; Perkins et al. 1986; Doroquez et al. 2014). Cilia present on different sensory neuron types are specialized both in morphology and function, and are generated and maintained via shared and cell-specific molecules and mechanisms (Perkins et al. 1986; Evans et al. 2006; Mukhopadhyay et al. 2007; Mukhopadhyay et al. 2008; Morsci and Barr 2011; Doroquez et al. 2014; Silva et al. 2017). The bilaterally symmetric pair of URX oxygen-sensing neurons in the C. elegans head (Figure 1A) is thought to be non-ciliated (Ward et al. 1975; Doroquez et al. 2014) but nevertheless exhibits intriguing morphological similarities with ciliated sensory neurons. URX dendrites extend to the nose where they terminate in large bulb-like complex structures (Ward et al. 1975; Doroquez et al. 2014; Cebul et al. 2020) (Figure 1A). These structures concentrate oxygen-sensing signaling molecules (Gross et al. 2014; Mclachlan et al. 2018) suggesting that similar to cilia, these structures are specialized for sensory functions. Microtubule growth events similar to those observed in ciliated sensory neurons were also reported at the distal dendritic regions of URX, implying the presence of a microtubule organizer such as a remodeled basal body (Harterink et al. 2018). Moreover, a subset of ciliary genes is expressed in URX (Kunitomo et al. 2005; Harterink et al. 2018; Mclachlan et al. 2018). We tested the hypothesis that URX dendrites contain cilia at their distal ends.

Wang W et al. (2009) Biochem Biophys Res Commun "Ced-9 inhibits Al-induced programmed cell death and promotes Al tolerance in tobacco."

Guo Y, Shao H, Pan J, Zhu M, Wang W, Chen H, Wang J, Bian H, Han N, Zheng K

[Biochem Biophys Res Commun, 2009]

Our previous data showed that apoptotic suppressors inhibit aluminum (Al)-induced programmed cell death (PCD) and promote Al tolerance in yeast cells, however, very little is known about the underlying mechanisms, especially in plants. Here, we show that the Caenorhabditis elegans apoptotic suppressor Ced-9, a Bcl-2 homologue, inhibited both the Al-induced PCD and Al-induced activity of caspase-like vacuolar processing enzyme (VPE), a crucial executioner of PCD, in tobacco. Furthermore, we show that Ced-9 significantly alleviated Al inhibition of root elongation, decreased Al accumulation in the root tip and greatly inhibited Al-induced gene expression in early response to Al, leading to enhancing the tolerance of tobacco plants to Al toxicity. Our data suggest that Ced-9 promotes Al tolerance in plants via inhibition of Al-induced PCD, indicating that conserved negative regulators of PCD are involved in integrated regulation of cell survival and Al-induced PCD by an unidentified mechanism.

Halic M et al. (2009) Mol Cell "22G-RNAs in transposon silencing and centromere function."

Moazed D, Halic M

[Mol Cell, 2009]

Three recent papers (Gu et al., 2009; Claycomb et al., 2009; van Wolfswinkel et al., 2009) provide evidence that links a new class of small RNAs and Argonaute-associated complexes to centromere function and genome surveillance.

Page KE et al. (2012) Metallomics "Aluminium exposure disrupts elemental homeostasis in Caenorhabditis elegans."

Killilea DW, Page KE, Lithgow GJ, White KN, McCrohan CR

[Metallomics, 2012]

Aluminium (Al) is highly abundant in the environment and can elicit a variety of toxic responses in biological systems. Here we characterize the effects of Al on Caenorhabditis elegans by identifying phenotypic abnormalities and disruption in whole-body metal homeostasis (metallostasis) following Al exposure in food. Widespread changes to the elemental content of adult nematodes were observed when chronically exposed to Al from the first larval stage (L1). Specifically, we saw increased barium, chromium, copper and iron content, and a reduction in calcium levels. Lifespan was decreased in worms exposed to low levels of Al, but unexpectedly increased when the Al concentration reached higher levels (4.8 mM). This bi-phasic phenotype was only observed when Al exposure occurred during development, as lifespan was unaffected by Al exposure during adulthood. Lower levels of Al slowed C. elegans developmental progression, and reduced hermaphrodite self-fertility and adult body size. Significant developmental delay was observed even when Al exposure was restricted to embryogenesis. Similar changes in Al have been noted in association with Al toxicity in humans and other mammals, suggesting that C. elegans may be of use as a model for understanding the mechanisms of Al toxicity in mammalian systems.

Chavez-Perez, Carlos et al. (2021) MicroPubl Biol

Rohacek, Alex M, Raizen, David M, Jafari, Niusha, Chavez-Perez, Carlos, Keenan, Brendan T

[MicroPubl Biol, 2021]

Like other animals, the nematode C. elegans exhibits reduced movement and sleep in response to sickness, which can be induced by exposure to high temperatures (Hill et al. 2014; Nelson et al. 2014) ultraviolet light (DeBardeleben et al. 2017), and other stressful exposures (Hill et al. 2014; Goetting et al. 2020). This response has been termed Stress/Sickness-Induced Sleep (SIS) (Hill et al. 2014; Trojanowski and Raizen 2016). Exposure to the stressor leads to quiescence in part via release of the cytokine Epidermal Growth Factor (EGF) (Hill et al. 2014; Konietzka et al. 2020), which is encoded by the gene lin-3 (Hill and Sternberg 1992). EGF activates the ALA and RIS neurons, which then release their respective neuropeptides to effect reduced movement and behavioral quiescence (Konietzka et al. 2020).

Yeon, Jihye et al. (2021) MicroPubl Biol

Sengupta, Piali, Takeishi, Asuka, Yeon, Jihye

[MicroPubl Biol, 2021]

Neuronal networks can achieve similar outputs via distinct underlying circuit mechanisms (Beverly et al., 2011; Marder et al., 2015; Saideman et al., 2007; Trojanowski et al., 2014; Wang et al., 2019). This degeneracy allows networks to maintain robustness without compromising functional flexibility (Cropper et al., 2016; Edelman and Gally, 2001). Since the contribution of degenerate neuronal pathways is likely to be revealed under defined genetic or environmental conditions, it is challenging to identify and describe the contributions of such pathways to neuronal circuit function.

Johnson, Christina K. et al. (2021) MicroPubl Biol

Miller, David D., Johnson, Christina K., Bianchi, Laura

[MicroPubl Biol, 2021]

MEC-4 and UNC-8 are subunits of the DEG/ENaC family of voltage-independent Na+ channels in C. elegans (Driscoll and Chalfie 1991, Canessa, Horisberger et al. 1993, Waldmann, Champigny et al. 1996, Waldmann, Champigny et al. 1997, de Weille, Bassilana et al. 1998, Waldmann and Lazdunski 1998). While MEC-4 is expressed in body touch neurons where it mediates the transduction of gentle touch sensation (Driscoll and Chalfie 1991, O'Hagan, Chalfie et al. 2005), UNC-8 is primarily expressed in motoneurons where it is involved in synaptic remodeling during development (Tavernarakis, Shreffler et al. 1997, Miller-Fleming, Petersen et al. 2016). Both MEC-4 and UNC-8 can be hyperactivated by genetic mutations that hinder channel closing, called (d) mutations (Driscoll and Chalfie 1991, Shreffler, Magardino et al. 1995, Goodman, Ernstrom et al. 2002, Wang, Matthewman et al. 2013). C. elegans neurons and Xenopus oocytes expressing these hyperactive variants of MEC-4 and UNC-8 undergo cell death due to uncontrolled flux of ions into the cell. Cell death in Xenopus oocytes and in cultured C. elegans neurons can be prevented by incubation with the DEG/ENaC channel blocker amiloride (Goodman, Ernstrom et al. 2002, Suzuki, Kerr et al. 2003, Wang, Matthewman et al. 2013).