Shen Q et al. (2009) Mol Cell Biol "Adenine nucleotide translocator cooperates with core cell death machinery to promote apoptosis in Caenorhabditis elegans."

Yang C, Xu Z, Xiao H, Gao Z, Qin F, Shen Q, Cui J

[Mol Cell Biol, 2009]

In Caenorhabditis elegans, the central cell-killing process is essentially controlled by the interplay of four apoptotic factors: EGL-1/BH3-only protein, CED-9/Bcl2, CED-4/Apaf1, and CED-3/caspase. In cells destined to die, EGL-1 binds to CED-9 and results in the release of CED-4 from the mitochondrion-tethered CED-9-CED-4 complex to the perinucleus, which facilitates processing of the CED-3 caspase to cause apoptosis. However, whether additional factors exist to regulate the cell-killing process remains largely unknown. We have identified here WAN-1, the C. elegans ortholog of mammalian adenine nucleotide translocator, as an important cell death regulator. Genetic inactivation of wan-1 significantly suppressed both somatic and germ line cell deaths in C. elegans. Consistently, chemical inhibition of WAN-1 activity also caused strong reduction of germ line apoptosis. WAN-1 localizes to mitochondria and can form complex with both CED-4 and CED-9. Importantly, the cell death initiator EGL-1 can disrupt the interaction between CED-9 and WAN-1. In addition, overexpression of WAN-1 induced ectopic cell killing dependently on the core cell death pathway. These findings suggest that WAN-1 is involved in the central cell-killing process and cooperates with the core cell death machinery to promote programmed cell death in C. elegans.

Qinfang Shen et al. (2008) "Adenine nucleotide translocator cooperates with core cell death machinery to control programmed cell death in C. elegans"

Zhiheng Xu, Qinfang Shen, Zhiyang Gao, Fengsong Qin, Chonglin Yang, Jie Cui

[2008]

"In C. elegans, the central cell-killing process is essentially controlled by the interplay of four apoptotic factors: EGL-1/BH3-only protein, CED-9/Bcl-2, CED-4/Apaf-1 and CED-3/caspase. In cells that are destined to die, the BH3-only proapoptotic protein EGL-1 is up regulated and binds to CED-9, resulting in the release of CED-4 from the mitochondria-tethered CED-9-CED-4 complex to perinucleus, which promotes the processing of CED-3 and leads to apoptosis. However, whether additional regulators exist to regulate the cell killing process together with these 4 apoptotic factors remains largely unknown. Here we have identified WAN-1, the C. elegans ortholog of mammalian adenine nucleotide translocator 1 (ANT1), as an important cell death regulator in C. elegans. WAN-1 localizes to mitochondria and forms complex with either CED-4 or CED-9 but not EGL-1. Importantly, the cell death initiator EGL-1 can disrupt the CED-9-WAN-1 complex. In activation of wan-1 by RNA interference significantly suppresses both somatic and germline apoptosis. Consistently, inhibition of WAN-1/ANT activity by Bongkrekic acid, an ANT-specific inhibitor, also leads to drastic suppression of germline apoptosis. These findings suggest that WAN-1/ANT is directly involved in the cell-killing process and cooperates with core cell death components to control the activation of apoptosis. Moreover, our results suggest that adenine nucleotide translocator functions evolutionarily to regulate cell death from C. elegans to humans."

Po MD et al. (2012) Neuron "Releasing the inner inhibition for axon regeneration."

Po MD, Calarco JA, Zhen M

[Neuron, 2012]

The adult mammalian central nervous system exhibits restricted regenerative potential. Chen etal. (2011) and El Bejjani and Hammarlund (2012) used Caenorhabditis elegans to uncover intrinsic factors that inhibit regeneration of axotomized mature neurons, opening avenues for potential therapeutics.

Kristin C Gunsalus et al. (2003) International Worm Meeting "RNAi Database and InFuGen: tools for functional genomics"

Wan-Chen Yueh, Apurva Narechania, Jerry Huang, Fabio Piano, Philip MacMenamin, Kristin C Gunsalus

[International Worm Meeting, 2003]

Different functional genomics efforts have been initiated in C. elegans, including RNAi phenotype, expression profile, and protein interaction mapping projects. We are developing Web-accessible database tools to facilitate the archival, distribution, navigation, and mining of these data. RNAiDB (www.rnai.org): RNAiDB is a database tool for the archival and analysis of RNAi-based results from large-scale studies. It presents a view of the genome centered around phenotypic analysis, is fully searchable, and provides a user-friendly interface for navigation with links to external database resources. RNAiDB uses the AceDB database engine and is easily integrated with WormBase through its compatible database models. We are extending the functionality of RNAiDB in several ways. To enhance flexibility for mining phenotypic data we are creating tools such as 'PhenoBlast', which ranks genes on the basis of their overall phenotypic similarities (thus providing a function analogous to that of BLAST for sequence searching). We have extended the RNAiDB data models to accommodate one-to-many mappings between RNAi experiments and potentially inhibited target genes based on sequence analyses such as ePCR or BLAST. We have also created a rich set of new data models for phenotypic scoring together with a comprehensive Web-based data entry system that allows users to record phenotypic data directly into the database as they are being scored in a controlled, systematic manner via a series of Web forms linked to the database. InFuGen: We have begun prototyping a second Web tool to facilitate the exploration of different types of functional genomics data in an integrated fashion, which we call "InFuGen" (Integrated Functional Genomics). The idea behind this tool is to provide the ability to visualize and navigate network relationships between genes based on correlations from a combination of different functional and genomic data such as phenotypic signatures, gene expression profiles, protein interaction maps, sequence similarity, domain composition, and functional annotations.

Silverstein NJ et al. (2017) Immunity "Interleukin-17: Why the Worms Squirm."

Huh JR, Silverstein NJ

[Immunity, 2017]

IL-17 is a cytokine known primarily for its role in inflammation. In a recent issue of Nature, Chen etal. (2017) demonstrate that IL-17 plays a neuromodulatory role in Caenorhabditis elegans by acting directly on neurons to amplify neuronal responses to stimuli and produce changes in animal behavior.

Artan M et al. (2016) Dev Cell "Heat FLiPs a Hormonal Switch for Longevity."

Lee SV, An SW, Artan M

[Dev Cell, 2016]

Temperature-sensing neurons in C.elegans reduce the life-shortening effects of high temperatures via steroid signaling. In this issue of Developmental Cell, Chen etal. (2016) elucidate the underlying mechanisms by which the transcription factor CREB induces the neuropeptide FLP-6 in the temperature-sensing neurons to counteract the life-shortening effects of high temperature.

Akin O et al. (2014) Cell "The shape of things to come."

Akin O, Zipursky SL

[Cell, 2014]

Surface receptors can link binding of ligands to changes in the actin-based cell cytoskeleton. Chia etal. and Chen etal. provide evidence for direct binding between the cytoplasmic tails ofreceptorsand the WAVE complex, a regulator of the actin nucleator Arp2/3 complex, which mighthelp to explain how environmental signals are translated into changes in morphology andmotility.

Chen X et al. (2015) Mol Neurodegener "Erratum to: Ethosuximide ameliorates neurodegenerative disease phenotypes by modulating DAF-16/FOXO target gene expression."

McCue HV, Chen X, Morgan A, Kashyap SS, Barclay JW, Kraemer BC, Burgoyne RD, Wong SQ

[Mol Neurodegener, 2015]

The original version of this article [1] unfortunately contained a mistake. The author list contained a spelling error for the author Hannah V. McCue. The original article has been corrected for this error. The corrected author list is given below:Xi Chen, Hannah V. McCue, Shi Quan Wong, Sudhanva S. Kashyap, Brian C. Kraemer, Jeff W. Barclay, Robert D. Burgoyne and Alan Morgan

Palikaras K et al. (2016) Bio Protoc "Measuring Oxygen Consumption Rate in Caenorhabditis elegans."

Palikaras K, Tavernarakis N

[Bio Protoc, 2016]

The rate of oxygen consumption is a vital marker indicating cellular function during lifetime under normal or metabolically challenged conditions. It is used broadly to study mitochondrial function (Artal-Sanz and Tavernarakis, 2009; Palikaras et al., 2015; Ryu et al., 2016) or investigate factors mediating the switch from oxidative phosphorylation to aerobic glycolysis (Chen et al., 2015; Vander Heiden et al., 2009). In this protocol, we describe a method for the determination of oxygen consumption rates in the nematode Caenorhabditis elegans.

Chen CH et al. (2021) STAR Protoc "Live-cell imaging of PVD dendritic growth cone in post-embryonic C.elegans."

Chen CH, Pan CL

[STAR Protoc, 2021]

Live-cell imaging analysis provides tremendous information for the study of cellular events such as growth cone migration in neuronal development. Here, we describe a protocol for live-cell imaging of migrating PVD dendritic growth cones in the nematode <i>C.elegans</i> by spinning-disk confocal microscopy. Fluorescently labeled growth cones and cytoskeletal proteins could be continuously observed for 4-6h in mid-stage larvae. This protocol is suitable for revealing the dynamic molecular and cellular events in dendrite and axon development of <i>C.elegans</i>. For complete details on the use and execution of this protocol, please refer to Chen etal. (2019).