Mitchell, J. et al. (2019) International Worm Meeting "The role of cadherins at sensory synapses."

Teschner, L., Agenor, V., Benedetti, K., Bi, V., VanHoven, M., Tang, A., Park, J., Andersen, K., Muqtadir, T., Ali, N, Mitchell, J.

[International Worm Meeting, 2019]

The nervous system mediates such fundamental processes as sensory perception. The faithful formation of neural circuits is required for all forms of sensory perception, and defects in the formation and structure of neural circuits are thought to underlie neurological disorders, such as schizophrenia and autism spectrum disorder. Cadherins are a large superfamily of transmembrane cell adhesion molecules widely known for the roles they play during development. Cadherins are also known for their role in providing structural support, and have been implicated in synapse formation and integrity. However, much remains to be learned about the roles of individual cadherins in the formation of sensory circuits. We sought to identify cadherins necessary for the formation and integrity of sensory synapses using the phasmid sensory circuit in C. elegans. Specifically, we focused on synaptic connections between PHB sensory neurons, and AVA interneurons. To determine if defects in cadherins affect sensory synapses, we utilized the split GFP-based trans-synaptic marker NLG-1 GRASP (Neuroligin-1 GFP Reconstitution Across Synaptic Partners). We screened mutants affecting C. elegans cadherin superfamily proteins to identify molecules with altered NLG-1 GRASP intensity. The mutants we tested include the Dachsous-like cadherin cdh-1; the Fat-like cadherins cdh-3 and cdh-4; the nematode-specific cadherins cdh-5, cdh-7, cdh-8, and cdh-10; the Flamingo/Stan cadherin cdh-6, and cdh-9, which is similar to DCad96Cb. We found modest decreases in NLG-1 GRASP intensity in the nematode-specific cadherins cdh-5 and cdh-8, and an approximately 50% decrease in NLG-1 GRASP intensity in cdh-6/Flamingo, which was previously shown to regulate synapse development in VD motorneurons by Najarro and colleagues (J. Neurosci, 2012). Interestingly, defects in cdh-6/Flamingo were present in L4, but not L1 animals, suggesting a later function for this gene at PHB-AVA synapses. Identifying roles for cadherins at sensory synapses will bring us closer to understanding the factors that may be playing roles in synaptic maintenance across an organism's lifetime, and may also help us better understand mechanisms whose dysfunction leads to neurological disorders.

Mitchell DL et al. (1979) J Gerontol "Synchronous growth and aging of Caenorhabditis elegans in the presence of fluorodeoxyuridine."

Stiles JW, Sanadi DR, Santelli J, Mitchell DL

[J Gerontol, 1979]

Fluorodeoxyuridine (FUdR), an inhibitor of DNA synthesis, was examined for its ability to prevent a synchronous population of C. elegans from reproducing without otherwise interfering with the organism's post-maturational development and aging. When a synchronized population was exposed to 400 micrometer FUdR just as the population reached sexual maturity, the FUdR induced complete sterility within five hours by preventing eggs from hatching. Any larvae that hatched from eggs made before the FUdR was added remained small in the presence of FUdR and were easily removed by filtration or sedimentation. FUdR-sterilized adults showed no morphological abnormalities. Age-associated changes seen in controls also occurred in FUdR-treated worms, including atrophy of the gonads, increased pigmentation, sluggishness and increased transparency. Life span was not shortened by FUdR treatment. Our observations suggest that treatment with FUdR under carefully controlled conditions is a reasonable way to maintain synchronously aging populations of C.

Mitchell PH et al. (2007) Pharmacogenomics J "The concentration-dependent effects of ethanol on Caenorhabditis elegans behaviour."

Hopper NA, Bull K, Holden-Dye L, Mitchell PH, Glautier S, O'Connor V

[Pharmacogenomics J, 2007]

The effects of ethanol on the brain are concentration dependent. Low concentrations (mM) intoxicate, while greater than 100 mM anaesthetize. Of most relevance to human alcohol addiction are mechanisms of intoxication. Previously, Caenorhabditis elegans has been employed in genetic screens to define effectors of intoxication. Here, we inform interpretation of these studies by providing evidence that ethanol rapidly equilibriates across C. elegans cuticle. Importantly, the effect of ethanol on muscle activity rapidly reaches steady-state, and the concentration-dependence of the effect is very similar in intact animals and exposed muscle. Thus the cuticle does not present an absorption barrier for ethanol, and furthermore the internal concentration is likely to approach that applied externally. Thus, modelling intoxication in C. elegans requires exposure to external ethanol less than 100 mM. Furthermore, the permeability of the cuticle to ethanol enables analysis of precisely controlled concentration-dependent effects of acute, chronic, and episodic ethanol exposure on behaviour.The Pharmacogenomics Journal advance online publication, 27 February 2007; doi:10.1038/sj.tpj.6500440.

Mitchell WA et al. (2001) Eur J Paediatr Neurol "Genomic structure of three CLN3-like genes in Caenorhabditis elegans."

Kuwabara P, Mitchell WA, Mole SE, Porter M

[Eur J Paediatr Neurol, 2001]

The genome of Caenorhabditis elegans is predicted to carry three genes similar to CLN3, the gene underlying juvenile neuronal ceroid lipofuscinosis. All three genes are transcribed and the genomic structure has been determined. The number and position of exons for two of the genes differ from that predicted from the genomic sequence, but no discrepancies with the genomic nucleotide sequence were found. Gene F07B10.1 (cln-3.1) is predicted to have 7 exons and to encode a protein of 424 amino acids. Gene C01G8.2 (cln-3.2) has 9 exons and encodes a protein of 435 amino acids. Gene ZC190.1 (cln-3.3) is predicted to have 9 exons and to encode a protein of 416 amino acids.

McGhee JD (1987) Biochemistry "Purification and characterization of a carboxylesterase from the intestine of the nematode Caenorhabditis elegans."

McGhee JD

[Biochemistry, 1987]

The major intestinal esterase from the nematode Caenorhabditis elegans has been purified to essential homogeneity. Starting from whole worms, the overall purification is 9000-fold with a 10% recovery of activity. The esterase is a single polypeptide chain of Mr 60,000 and is stoichiometrically inhibited by organophosphates. Substrate preferences and inhibition patterns classify the enzyme as a carboxylesterase (EC 3.1.1.1), but the physiological function is unknown. The sequence of 13 amino acid residues at the esterase N- terminus has been determined. This partial sequence shows a surprisingly high degree of similarity to the N-terminal sequence of two carboxylesterases recently isolated from Drosophila mojavensis [Pen, J., van Beeumen, J., & Beintema, J. J. (1986) Biochem. J. 238, 691-699].

Murakami S et al. (1999) Curr Biol "Life extension and stress resistance in Caenorhabditis elegans modulated by the tkr-1 gene."

Johnson TE, Murakami S

[Curr Biol, 1999]

In this Brief Communication, which appeared in the 14 September 1998 issue of Current Biology, the UV dose was reported erroneously. The dose reported was 20 J/m2 but the actual dose used was 0.4 J/cm2. Also, the gene formally referred to as tkr-1 has since been renamed old-1 (overexpression longevity determination).

Ramos CG et al. (2014) J Bacteriol "Retraction for Ramos et al., MtvR is a global small noncoding regulatory RNA in Burkholderia cenocepacia."

Feliciano JR, da Costa PJ, Ramos CG, Grilo AM, Leitao JH

[J Bacteriol, 2014]

Volume 195, no. 16, p. 35143523, 2013. A number of problems related to images published in this paper have been brought to our attention. Figure 1D contains duplicated images in lanes S and LE, and Fig. 4D and 6B contain images previously published in articles in this journal and in Microbiology and Microbial Pathogenesis, i.e., the following: C. G. Ramos, S. A. Sousa, A. M. Grilo, J. R. Feliciano, and J. H. Leitao, J. Bacteriol. 193:15151526, 2011. doi:10.1128/JB.01374-11. S. A. Sousa, C. G. Ramos, L. M. Moreira, and J. H. Leitao, Microbiology 156:896908, 2010. doi:10.1099/mic.0.035139-0. C. G. Ramos, S. A. Sousa, A. M. Grilo, L. Eberl, and J. H. Leitao, Microb. Pathog. 48:168177, 2010. doi: 10.1016/j.micpath.2010.02.006. Therefore, we retract the paper. We deeply regret this situation and apologize for any inconvenience to the editors and readers of Journal of Bacteriology, Microbial Pathogenesis, and Microbiology.

Nillegoda NB et al. (2015) Nature "Crucial HSP70 co-chaperone complex unlocks metazoan protein disaggregation."

Berynskyy M, Morimoto RI, Bukau B, Stengel F, Kirstein J, Szlachcic A, Arnsburg K, Stank A, Scior A, Nillegoda NB, Gao X, Guilbride DL, Aebersold R, Wade RC, Mayer MP

[Nature, 2015]

Protein aggregates are the hallmark of stressed and ageing cells, and characterize several pathophysiological states. Healthy metazoan cells effectively eliminate intracellular protein aggregates, indicating that efficient disaggregation and/or degradation mechanisms exist. However, metazoans lack the key heat-shock protein disaggregase HSP100 of non-metazoan HSP70-dependent protein disaggregation systems, and the human HSP70 system alone, even with the crucial HSP110 nucleotide exchange factor, has poor disaggregation activity in vitro. This unresolved conundrum is central to protein quality control biology. Here we show that synergic cooperation between complexed J-protein co-chaperones of classes A and B unleashes highly efficient protein disaggregation activity in human and nematode HSP70 systems. Metazoan mixed-class J-protein complexes are transient, involve complementary charged regions conserved in the J-domains and carboxy-terminal domains of each J-protein class, and are flexible with respect to subunit composition. Complex formation allows J-proteins to initiate transient higher order chaperone structures involving HSP70 and interacting nucleotide exchange factors. A network of cooperative class A and B J-protein interactions therefore provides the metazoan HSP70 machinery with powerful, flexible, and finely regulatable disaggregase activity and a further level of regulation crucial for cellular protein quality control.

Miller DM et al. (1992) Worm Breeder's Gazette "unc-4 LacZ Expression in A-Type Motor Neurons"

Miller DM, Niemeyer CJ

[Worm Breeder's Gazette, 1992]

unc-4 LacZ expression in A-type motor neurons David M. Miller and Charles J. Niemeyer, Dept. of Cell Biology, Duke Univ. Medical Ctr, Durham, NC 27710

Sommer RJ et al. (1994) Worm Breeder's Gazette "Evolution of Vulva-Formation: Part II: Species With a Central Vulva"

Sommer RJ, Sternberg PW

[Worm Breeder's Gazette, 1994]

Evolution of vulva-formation: Part II: Species with a central vulva Ralf J. Sommer & Paul W. Sternberg, California Institute of Technology, Division of Biology 156-29, Pasadena, CA 91125