Larsen PL (2001) Nat Genet "Asking the age-old questions."

Larsen PL

[Nat Genet, 2001]

Control of lifespan in Caenorhabditis elegans by the DAF-2 insulin-like signaling pathway requires daf-16. which encodes a member of the forkhead family of transcription factors. A new study provides evidence that DAF-2 negatively regulates DAF-16 activity by promoting its retention in the cytoplasm. But, constitutive targeting of DAF-16 to the nucleus is not sufficient to extend lifespan, revealing a new layer of complexity in the genetic control of aging in the nematode.

Johnson KA et al. (1996) Nature "Protein kinases. Twitching worms catch S100."

Quiocho FA, Johnson KA

[Nature, 1996]

Springtime finds hopeful anglers baiting hungry fish with twitching worms, both live and artificial. Fish prefer the large annelids, but Kemp and coworkers have knotted on their lines the small, alluring nematode Caenorhabditis elegans, which twitches spasmodically when the aptly named protein twitchin goes missing from its muscle cells. And they've caught a big one! On page 636 of this issue, these authors report that the giant protein kinase twitchin, which has a relative molecular mass of 750K and is found in nematode muscle cells, and the protein S100A1(2), a member of the S100 family of calcium-binding proteins, make up a third new calcium-regulated system in muscle which may be of great importance in organizing muscle structure and maintaining its resting tension. They show that a fragment of twitchin containing the autoinhibited kinase domain is specifically activated in a calcium-dependent and zinc-enhanced manner by S100A1(2), but not by the S100B(2) isoform with which it shares 60 percent homology....

Han X et al. (2010) Nat Cell Biol "Meiotic kinetochores get pushed aside by a CLS act."

Han X, Srayko M

[Nat Cell Biol, 2010]

Kinetochores link microtubules to DNA and provide force critical for chromosome segregation in mitosis. New data show that kinetochores are not necessary for acentrosomal meiotic chromosome segregation in Caenorhabditis elegans. Instead, CLS-2 (CLASP) generates a mid-zone bundle of microtubules that are suggested to act in pushing the chromosomes apart.

Burglin TR et al. (1991) Nature "Nematode homeobox cluster."

Coulson AR, Burglin TR, Waterston RH, Mueller F, Wittmann C, Hawkins NC, Schaller CWD, McGhee JD, Ruvkun GB

[Nature, 1991]

Clusters of Antennapedia-like homeobox genes have been found in Drosophila and in vertebrates (see ref. 2 for review) that show a remarkable similarity of organization and expression. Intriguingly, the order of the homeobox genes along the chromosome corresponds to the order of expression domains along the anterior-posterior axis of the animal. A large-scale screening for homeobox-containing genes in the nematode Caenorhabditis elegans did not initially reveal such clusters. But, as the C. elegans map has been further refined, a previously unmapped small contiguous set of cosmid clones (locus No. 38 in ref. 2) containing two homeobox genes, ceh-13 (ref. 4) and ceh-15 (hom-2/3 in ref. 5; C. Kenyon personal communication) has now been located on chromosome III, to the left of the homeobox genes mab-5 (ref. 6) and ceh-11 (refs 4, 7; see figure). These four genes form a cluster of Antennapedia-like homeobox genes that appear to maintain the same anterior-posterior ordering found in flies and

Hengartner MO (1998) Nature "Apoptosis. Death cycle and Swiss army knives."

Hengartner MO

[Nature, 1998]

Cytochrome c leads a double life. When a cell is called on to commit apoptotic suicide, cytochrome c relocalizes from the mitochondria to the cytosol. There, it helps to activate the foot-soldiers of apoptosis - the death proteases known as caspases. How cytochrome c escapes from the mitochondria is still a matter of debate, but it is clear that certain elements within the apoptotic regulatory hierarchy do not condone such behavior. In particular, overexpression of the cell-death suppressors Bcl-2 and Bcl-xL prevents the release of cytochrome c, suggesting that these proteins act upstream of cytochrome c in the pathway to death. However, on pages 449 and 496 of this issue, Zhivotovsky et al. and Rosse et al. show that Bcl-2 can also protect cells downstream of cytochrome c release, forcing a re-evaluation of this newly acquired dogma.

Habeos I et al. (2001) Trends Endocrinol Metab "Type 2 diabetes mellitus and worm longevity: a transcriptional link to cure?"

Habeos I, Papavassiliou AG

[Trends Endocrinol Metab, 2001]

In Caenorhabditis elegans, an insulin-like signalling pathway culminates in a transcription factor (TF) that is homologous to a subfamily of Tps responsible for the regulation of a subset of insulin-responsive genes in humans. Under harsh conditions, C. elegans reduces signalling through this pathway and arrests developmentally in a manner that is similar to the metabolic syndrome of humans. We propose that an understanding of this pathway could lead to drugs with optimal potency and selectivity in the treatment of type 2 diabetes mellitus.

Drescher U (1996) Nature "Netrins find their receptor."

Drescher U

[Nature, 1996]

What guides migrating nerve axons to their correct targets during development? This is one of the basic issues in developmental neurobiology, and chemoattraction has long been thought to be involved. A tangible answer began to emerge with the demonstration that explants of rat spinal floorplate promoted the outgrowth of axons from commissural neurons, and caused these axons to turn. Subsequently, the specific factors concerned in axon turning were identified. These factors, called netrin-1 and netrin-2, are phlogenetically conserved molecules related to the product of the unc-6 gene in Caenorhabditis elegans.

Pennisi E (1996) Science "Worm genes imply a master clock."

Pennisi E

[Science, 1996]

What 's the secret to long life? For the nematode Caenorhabditis elegans, it's slow, easy living, in which all life's events occur in a leisurely rhythm, according to work described on page 1010 of this issue. The new research, by Siegfried Hekimi and Bernard Lakowski of McGill University in Montreal, identifies four genes that, when mutated, can make these worms use energy more efficiently, feed and swim at a slower pace-and live many times their normal life-span. Some of the experimental nematodes lived for almost 2 months, far longer than their expected 9 days.

Emmons SW et al. (1999) Nature "Signal transduction. Mating, channels and kidney cysts."

Somlo S, Emmons SW

[Nature, 1999]

Advances in human genetics have meant that the genes mutated in human diseases can be identified exclusively by their location in the genome. But how do we work out the cellular functions of the associated protein products? Reports on pages 383 and 386 of this issue begin to address this problem for two proteins - polycystin-1 (PKD1) and polycystin-2 (PKD2) - that are defective in human kidney disease. From their studies of the nematode worm Caenorhabditis elegans, Barr and Sternberg present evidence that homologues of the polycystins act together in a signal-transduction pathway in sensory neurons. Chen et al., by contrast, have used an oocyte-expression system in the from Xenopus laevis to show that a homologue of PKD2 is associated with the activity of a cation channel. These results support the hypothesis that polycystin-related proteins belong to a hitherto unknown class of signal-transduction molecules.

Heo W et al. (2022) BMB Rep "The CCAAT-box transcription factor, NF-Y complex, mediates the specification of the IL1 neurons in C. elegans."

Yu Y, Lee JH, Heo W, Hwang H, Oh SH, Kim K, Kim J

[BMB Rep, 2022]

Neuronal differentiation is highly coordinated through a cascade of gene expression, mediated via interactions between transacting transcription factors and cis-regulatory elements of their target genes. However, the mechanisms of transcriptional regulation that determine neuronal cell-fate are not fully understood. Here, we show that the nuclear transcription factor Y (NF-Y) subunit, NFYA-1, is necessary and sufficient to express the flp-3 neuropeptide gene in the IL1 neurons of C. elegans. flp-3 expression is decreased in dorsal and lateral, but not ventral IL1s of nfya-1 mutants. The expression of another terminally differentiated gene, eat-4 vesicular glutamate transporter, is abolished, whereas the unc-8 DEG/ENaC gene and pan-neuronal genes are expressed normally in IL1s of nfya-1 mutants. nfya-1 is expressed in and acts in IL1s to regulate flp-3 and eat-4 expression. Ectopic expression of NFYA-1 drives the expression of flp-3 gene in other cell-types. Promoter analysis of IL1-expressed genes results in the identification of several cisregulatory motifs which are necessary for IL1 expression, including a putative CCAAT-box located in the flp-3 promoter that NFYA-1 directly interacts with. NFYA-1 and NFYA-2, together with NFYB-1 and NFYC-1, exhibit partly or fully redundant roles in the regulation of flp-3 or unc-8 expression, respectively. Taken together, our data indicate that the NF-Y complex regulates neuronal subtype-specification via regulating a set of terminal-differentiation genes.