Wang, Lei et al. (2021) International Worm Meeting "Glial mediators of K+ and Cl- transport shape C. elegans olfaction and taste"

Graziano, Bianca, Encalada, Nicole, Bianchi, Laura, Wang, Lei

[International Worm Meeting, 2021]

Anosmia is among the most prevalent symptom of SARS-CoV-2 infection. Interestingly though, the SARS-CoV-2 virus infects the olfactory supporting cells, rather than the primary sensory neurons themselves. These recent findings have underscored the importance of the supporting cells in olfaction. However, very little is known about the mechanisms underlying the regulation of olfaction by the supporting cells. In C. elegans, the Amphid sheath (Amsh) glial cells are the supportive cells of the amphid sensory apparatus, sharing with mammalian olfactory supporting cells general function and expression of the homologs of the SARS-CoV-2 viral entry proteins ACE2 and TMPRSS2. To understand the contribution of the Amsh glia to sensory function, our lab has taken the unbiased approach of sequencing the mRNA extracted from these cells. Among the ~1,000 glial-enriched genes, we identified 14 ion channel and transporter genes with 2.7- to 29.6-fold mRNA enrichment in Amsh glia as compared to other cells. To determine whether these channels and transporter genes are needed for sensory behaviors, we performed behavioral assays on knock-outs and Amsh cell specific knock-downs. Our results support the predominant requirement of glial K+ and Cl- channels and transporters for the response to isoamyl alcohol, octanol, diacetyl, and NaCl. Given, the recent report that Amsh glia function as odorant receptor cells, Ca2+ imaging experiments are underway to determine whether these channels and transporters alter the response of Amsh glia or sensory neurons (or both) to these sensory cues. Taken together, our findings expand on our understanding of the mechanisms underlying the contribution of Amsh glia to sensory perception in C. elegans; mechanisms that might be conserved from worm to man.

Infarinato N (2019) J Cell Biol "Xiaochen Wang: Building up our understanding of breaking down."

Infarinato N

[J Cell Biol, 2019]

Wang studies lysosomal degradation pathways using <i>C. elegans</i> as a model system.

Wang JT et al. (2014) Curr Biol "P granules."

Wang JT, Seydoux G

[Curr Biol, 2014]

Wang and Seydoux discuss the functional importance of P granules - the germline-specific RNA granules of C. elegans.

Hall DH et al. (1994) Worm Breeder's Gazette "Cytology of Degenerin-Induced Cell Death in the PVM Neuron"

Gong L, Driscoll MA, Gu GQ, Hall DH, Chalfie M

[Worm Breeder's Gazette, 1994]

Cytology of degenerin-induced cell death in the PVM neuron David H. Hall, Guoqiang Gu+, Lei Gong#, Monica Driscoll#, and Martin Chalfie+, * Dept. Neuroscience, Albert Einstein College of Medicine, Bronx, N.Y. 10461 + Dept. Biological Sciences, Columbia University, New York, N.Y. 10027 # Dept. Molecular Biology and Biochemistry, Rutgers University, Piscataway, N.J. 08855

Parrish, Angela et al. (2011) International Worm Meeting "Incorporating Unnatural Amino Acids in C. elegans."

Parrish, Angela, Xiang, Zheng, She, Xingyu, Dillin, Andrew, Coin, Irene, Wang, Lei

[International Worm Meeting, 2011]

Technologies to refine the study of protein interaction and localization in live organisms can be a key driving force for new research. One recent technology uses the cell's translation machinery to insert amino acids with novel functional groups at specific residues [1]. Amino acid residues of interest can be replaced by unnatural amino acids with various attributes, such as photo-crosslinking or environmentally sensitive fluorescence. By applying this technique, the role of certain sites of a protein in ligand binding or protein docking can be studied precisely, potentially by capturing an interaction that is transient using crosslinking. Proteins of interest could be fluorescently tagged by mutagenesis of a single amino acid, rather than appending an entire protein. The basis of this technology is the introduction of a tRNA and an aminoacyl-tRNA synthetase from another kingdom of life, which functions with the C. elegans translation machinery to insert an unnatural amino acid in response to a unique codon. We use the amber stop codon (UAG) to eliminate competition between native and introduced tRNAs in the ribosome during translation. The introduced tRNA has a corresponding anticodon mutation to recognize the altered codon, while the cognate aminoacyl-tRNA synthetase has been evolved to charge a specific unnatural amino acid on the mutant tRNA. The unnatural amino acid is supplied in the media. Expression of all the system components leads to the incorporation of an unnatural amino acid at the specified site of the growing polypeptide chain. To develop this system in C. elegans, tRNA/aminoacyl-tRNA synthetase pairs were assessed to find candidates that express functional and aminoacylated tRNAs. Using body wall muscle as a pilot tissue, the components of the system were validated using a mutagenized fluorescent protein as a reporter for unnatural amino acid incorporation, and quantitative expression data was collected for several unnatural amino acids using a mutagenized firefly luciferase reporter. Further study into the potential functions of this tool includes suppressing amber alleles of C. elegans genes. In the future, this system could be used for a variety of experiments, including tissue specific CHIP or visualization of protein interactions in live animals. [1] Expanding the genetic code for biological studies. Wang, Q., Parrish, A.R., Wang, L. Chem Biol. 2009 16(3): 323-36.

Rashid S et al. (2017) Dev Cell "Packing on the Pounds in Response to Bacterial Growth Conditions."

Rashid S, MacNeil LT

[Dev Cell, 2017]

Reporting in Nature Cell Biology, Lin and Wang (2017) show that bacterial methyl metabolism impacts host mitochondrial dynamics and lipid storage in C.elegans. The authors propose a model whereby bacterial metabolic products regulate a nuclear hormone receptor that promotes lipid accumulation through expression of a secreted Hedgehog-like protein.

Munro E (2017) Dev Cell "Protein Clustering Shapes Polarity Protein Gradients."

Munro E

[Dev Cell, 2017]

In this issue of Developmental Cell, Dickinson etal. (2017) and Rodriguez etal. (2017), along with Wang etal. (2017) in Nature Cell Biology, show how PAR protein oligomerization can dynamically couple protein diffusion and transport by cortical flow to control kinase activity gradients and polarity in the C.elegans zygote.

Vincenz L et al. (2014) Cell "Sugarcoating ER Stress."

Hartl FU, Vincenz L

[Cell, 2014]

The hexosamine biosynthetic pathway (HBP) generates metabolites for protein N- and O-glycosylation. Wang et al. and Denzel et al. report a hitherto unknown link between the HBP and stress in the endoplasmic reticulum. These studies establish the HBP as a critical component of the cellular machinery of protein homeostasis.

Sural S (2023) Trends Genet "Protecting axons in grandchildren."

Sural S

[Trends Genet, 2023]

Prenatal exposure to environmental agents can influence the fitness of not only the fetus, but also subsequent generations. In a recent study, Wang et al. demonstrated that feeding ursolic acid (UA), a plant-derived compound, to Caenorhabditis elegans mothers during their reproductive period prevented neurodegeneration in not only their offspring, but also the F2 progeny.

Spalthoff C et al. (2016) Neuron "Sensing pH with TMCs."

Gopfert MC, Spalthoff C

[Neuron, 2016]

Transmembrane channel-like (TMC) proteins have been implicated in hair cell mechanotransduction, Drosophila proprioception, and sodium sensing in the nematode C.elegans. In this issue of Neuron, Wang etal. (2016) report that C.elegans TMC-1 mediates nociceptor responses to high pH, not sodium, allowing the nematode to avoid strongly alkaline environments in which most animals cannot survive.