Correction for 'Long-term C. elegans immobilization enables high resolution developmental studies in vivo' by Simon Berger et al., Lab Chip, 2018, 18, 1359-1368.
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.
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.
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.
Upon endocytosis transmembrane cargo can be recycled for re-use or degraded via the Lysosome. Physically segregated microdomains on the sorting endosome direct transmembrane cargo to the appropriate route, and are influenced by stress and nutritional status of the cell. Keeping these microdomains physically distinct yet flexible is important for their functions and likely key to responding to changes in nutritional status. RME-8, an Hsc70 co-chaperone is an important endosomal regulator that maintains segregated microdomains and balances recycling and degradative activities on the sorting endosome. In the absence of RME-8 microdomains converge and cargo is missorted. Mutations in RME-8 are also associated with neurodegenerative disease in Humans such Parkinson's disease and essential tremors. As the activity of Hsp70 is specified by its cognate DNAJ protein, it has been proposed that RME-8 directs the uncoating activity of Hsp70 to limit the degradative domain on endosomes to promote recycling activities. While RME-8 represents an important endosomal regulator balancing recycling and degradative activities, how RME-8 itself is regulated has been unclear. Given the ancient origins of the DNAJ/DNAK pairing we analyzed the evolution of the RME-8 sequence to provide insight into important functional domains. We found RME-8 and its IWN and DNAJ domains to be remarkably conserved throughout Eukarya with notable absences in Fungi and Gymnosperms. Moreover, we identified new potential domains of interest. To better understand the mechanism of RME-8's function in light of the RME-8/SNX-1 interaction and potential autoinhibition, we performed structure-function analysis of RME-8. We found that the region between the lipid binding domain and the DNAJ domain is important for RME-8 endosomal recruitment from the cytoplasm, while the C-terminal IWN3 and IWN4 domains are required for RME-8 microdomain positioning. Using a directed evolution approach, we define an intramolecular IWN4/DNAJ-domain interaction that informs RME-8's interaction with SNX-1 and its uncoating activity toward ESCRT-0. We present a model whereby SNX-1 controls the oligomerization status of RME-8, its position on the endosome, and productive exposure of the DNAJ domain for uncoating reactions in both the recycling and degradative sorting domains.
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.
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.