Stone AL et al. (1999) J Protein Chem "Structure-function analysis of the ADAM family of disintegrin-like and metalloproteinase-containing proteins (review)."

Sang QX, Stone AL, Kroeger M

[J Protein Chem, 1999]

The ADAMs belong to a disintegrin-like and metalloproteinase-containing protein family that are zinc-dependent metalloproteinases. These proteins share all or some of the following domain structure: a signal peptide, a propeptide, a metalloproteinase, a disintegrin, a cysteine-rich, and an epidermal growth factor (EGF)-like domains, a transmembrane region, and a cytoplasmic tail. ADAMs are widely distributed in many organs, tissues, and cells, such as brain, testis, epididymis, ovary, breast, placenta, liver, heart, lung, bone, and muscle. These proteins are capable of four potential functions: proteolysis, adhesion, fusion, and intracellular signaling. Because the number of ADAM genes has grown rapidly and the biological functions of most members are unclear, this review analyzes the protein structures and functions, their activation and processing, their known and potential activities, and their evolutionary relationships. A sequence alignment of human ADAMs is compiled and their homology and physical data are calculated. The conceivable functions of ADAMs in reproduction, development, and diseases are also discussed.

Stone CE et al. (2009) Dev Biol "Lipocalin signaling controls unicellular tube development in the Caenorhabditis elegans excretory system."

Stone CE, Hall DH, Sundaram MV

[Dev Biol, 2009]

Unicellular tubes or capillaries composed of individual cells with a hollow lumen perform important physiological functions including fluid or gas transport and exchange. These tubes are thought to build intracellular lumina by polarized trafficking of apical membrane components, but the molecular signals that promote luminal growth and luminal connectivity between cells are poorly understood. Here we show that the lipocalin LPR-1 is required for luminal connectivity between two unicellular tubes in the Caenorhabditis elegans excretory (renal) system, the excretory duct cell and pore cell. Lipocalins are a large family of secreted proteins that transport lipophilic cargos and participate in intercellular signaling. lpr-1 is required at a time of rapid luminal growth, it is expressed by the duct, pore and surrounding cells, and it can function cell non-autonomously. These results reveal a novel signaling mechanism that controls unicellular tube formation, and provide a genetic model system for dissecting lipocalin signaling pathways.

Stone S et al. (2006) Hum Mol Genet "TBC1D1 is a candidate for a severe obesity gene and evidence for a gene/gene interaction in obesity predisposition."

Gutin A, Riley R, Abkevich V, Skolnick MH, He G, Jammulapati S, Shattuck D, Iliev D, Tran T, Gress R, Lanchbury JS, Timms K, Hunt SC, Frank D, Trem D, Neff CD, Adams TD, Frech GC, Russell DL, Stone S

[Hum Mol Genet, 2006]

The molecular etiology of obesity predisposition is largely unknown. Here, we present evidence that genetic variation in TBC1D1 confers risk for severe obesity in females. We identified a coding variant (R125W) in TBC1D1 that segregated with the disease in 4p15-14-linked obesity pedigrees. In cases derived from pedigrees with the strongest linkage evidence, the variant was significantly associated with obesity (P=0.000007) and chromosomes carrying R125W accounted for the majority of the evidence that originally linked 4p15-14 with the disease. In addition, by selecting families that segregated R125W with obesity, we were able to generate highly significant linkage evidence for an obesity predisposition locus at 4q34-35. This result provides additional and confirming evidence that R125W affects obesity susceptibility, delimits the location of an obesity gene at 4q34-35 and identifies a gene/gene interaction that influences the risk for obesity predisposition. Finally, although the function of TBC1D1 is unknown, the protein is structurally similar to a known regulator of insulin-mediated Glut4 translocation.

Stone S et al. (1993) Gene "A Caenorhabditis elegans act-4::lacZ fusion: use as a transformation marker and analysis of tissue-specific expression."

Stone S, Shaw JE

[Gene, 1993]

A plasmid vector that serves as a dominant marker for isolating transformed animals in Caenorhabditis elegans has been constructed as a translational fusion of the C. elegans act-4 gene (encoding actin) and the Escherichia coli lacZ gene. This gene fusion can be used as a marker in transformation rescue experiments in any fertile strain of C. elegans. Progeny of animals injected with the act-4=lacZ fusion vector are stained histochemically with XGa1, and transformants turn blue. The internal eggs of stained animals remain viable, allowing recovery of the transformed strain. When the act-4=lacZ vector is co-injected with an unselected plasmid with which it shares some sequence homology, most transformants that are recovered by screening for expression of the act-4=lacZ fusion contain both plasmids. Production of active betaGal in animals transformed with the act-4=lacZ gene fusions appears to be limited to certain tissues. A chimeric gene that contains the 5' and 3' regions of act-4 is expressed strongly in the body-wall muscles, vulval muscles, and spermathecae. Addition of the internal portion of act-4, including the protein-coding region and introns, to this chimeric gene leads to additional lacZ expression in the pharynx.

Schulze J et al. (2012) Evodevo "Plectus - a stepping stone in embryonic cell lineage evolution of nematodes."

Schulze J, Uenk J, Houthoofd W, Schierenberg E, Vangestel S

[Evodevo, 2012]

UNLABELLED: ABSTRACT: BACKGROUND: Recent studies have challenged the widespread view that the pattern of embryogenesis found in Caenorhabditis elegans (clade 9) is characteristic of nematodes in general. To understand this still largely unexplored landscape of developmental events, we set out to examine more distantly related nematodes in detail for temporospatial differences in pattern formation and cell specification. Members of the genus Plectus (clade 6) seem to be suitable candidates to show variety, with certain idiosyncratic features during early development and the convenient availability of cultivatable species. METHODS: The study was conducted using 4-D lineage analysis, 3-D modeling of developing embryos and laser-induced ablation of individual blastomeres. RESULTS: Detailed cell lineage studies of several Plectus species reveal that pattern formation and cell fate assignment differ markedly from C. elegans. Descendants of the first somatic founder cell S1 (AB) - but not the progeny of other founder cells - demonstrate extremely variable spatial arrangements illustrating that here distinct early cell-cell interactions between invariant partners, as found in C. elegans, cannot take place. Different from C. elegans, in Plectus alternative positional variations among early S1 blastomeres resulting in a 'situs inversus' pattern, nevertheless give rise to adults with normal left-right asymmetries. In addition, laser ablations of early blastomeres uncover inductions between variable cell partners. CONCLUSIONS: Our results suggest that embryonic cell specification in Plectus is not correlated with cell lineage but with position. With this peculiarity, Plectus appears to occupy an intermediate position between basal nematodes displaying a variable early development and the C. elegans-like invariant pattern. We suggest that indeterminate pattern formation associated with late, position-dependent fate assignment represents a plesiomorphic character among nematodes predominant in certain basal clades but lost in derived clades. Thus, the behavior of S1 cells in Plectus can be considered an evolutionary relict in a transition phase between two different developmental strategies.

Jovelin R et al. (2016) Worm "Hitting two birds with one stone: The unforeseen consequences of nested gene knockouts in Caenorhabditis elegans."

Jovelin R, Cutter AD

[Worm, 2016]

Nested genes represent an intriguing form of non-random genomic organization in which the boundaries of one gene are fully contained within another, longer host gene. The C. elegans genome contains over 10,000 nested genes, 92% of which are ncRNAs, which occur inside 16% of the protein coding gene complement. Host genes are longer than non-host coding genes, owing to their longer and more numerous introns. Indel alleles are available for nearly all of these host genes that simultaneously alter the nested gene, raising the possibility of nested gene disruption contributing to phenotypes that might be attributed to the host gene. Such dual-knockouts could represent a source of misinterpretation about host gene function. Dual-knockouts might also provide a novel source of synthetic phenotypes that reveal the functional effects of ncRNA genes, whereby the host gene disruption acts as a perturbed genetic background to help unmask ncRNA phenotypes.

Lordumrongkiat N et al. (2022) Sci Rep "HydroZitLa inhibits calcium oxalate stone formation in nephrolithic rats and promotes longevity in nematode Caenorhabditis elegans."

Ma-On C, Lordumrongkiat N, Boonla C, Jindatip D, Leelahavanichkul A, Chotechuang N, Prasanth MI, Tencomnao T, Chuenwisad K

[Sci Rep, 2022]

Low fluid intake, low urinary citrate excretion, and high oxidative stress are main causative factors of calcium oxalate (CaOx) nephrolithiasis. HydroZitLa contains citrate and natural antioxidants and is developed to correct these three factors simultaneously. Antioxidants theoretically can prolong the lifespan of organisms. In this study, we preclinically investigated the antilithogenic, lifespan-extending and anti-aging effects of HydroZitLa in HK-2 cells, male Wistar rats, and Caenorhabditis elegans. HydroZitLa significantly inhibited CaOx crystal aggregation in vitro and reduced oxidative stress in HK-2 cells challenged with lithogenic factors. For experimental nephrolithiasis, rats were divided into four groups: ethylene glycol (EG), EG + HydroZitLa, EG + Uralyt-U, and untreated control. CaOx deposits in kidneys of EG + HydroZitLa and EG + Uralyt-U rats were significantly lower than those of EG rats. Intrarenal expression of 4-hydroxynonenal in EG + HydroZitLa rats was significantly lower than that of EG rats. The urinary oxalate levels of EG + HydroZitLa and EG + Uralyt-U rats were significantly lower than those of EG rats. The urinary citrate levels of EG + HydroZitLa and EG + Uralyt-U rats were restored to the level in normal control rats. In C. elegans, HydroZitLa supplementation significantly extended the median lifespan of nematodes up to 34% without altering feeding ability. Lipofuscin accumulation in HydroZitLa-supplemented nematodes was significantly lower than that of non-supplemented control. Additionally, HydroZitLa inhibited telomere shortening, p16 upregulation, and premature senescence in HK-2 cells exposed to lithogenic stressors. Conclusions, HydroZitLa inhibited oxidative stress and CaOx formation both in vitro and in vivo. HydroZitLa extended the lifespan and delayed the onset of aging in C. elegans and human kidney cells. This preclinical evidence suggests that HydroZitLa is beneficial for inhibiting CaOx stone formation, promoting longevity, and slowing down aging.

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.