Biphasic adaptation to osmotic stress in the C. elegans germ line

Abstract

Cells respond to environmental stress in multiple ways. In the germ line, heat shock and nutritive stress trigger the assembly of large ribonucleoprotein (RNP) granules via liquid-liquid phase separation (LLPS). The RNP granules are hypothesized to maintain the quality of oocytes during stress. The goal of this study was to investigate the cellular response to glucose in the germ line and determine if it is an osmotic stress response. We found that exposure to 500 mM glucose induces the assembly of RNP granules in the germ line within 1 h. Interestingly, the RNP granules are maintained for up to 3 h; however, they dissociate after longer periods of stress. The RNP granules include processing body and stress granule proteins, suggesting shared functions. Based on several lines of evidence, the germ line response to glucose largely appears to be an osmotic stress response, thus identifying osmotic stress as a trigger of LLPS. Although RNP granules are not maintained beyond 3 h of osmotic stress, the quality of oocytes does not appear to decrease after longer periods of stress, suggesting a secondary adaptation in the germ line. We used an indirect marker of glycerol and observed high levels after 5 and 20 h of glucose exposure. Moreover, in germ lines, glycerol levels are reduced concomitant with RNP granules being maintained for an extended period. We speculate that increased glycerol levels may function as a secondary osmoregulatory adaptive response in the germ line, following a primary response of RNP granule assembly.

Pediococcus acidilactici CECT9879 (pA1c) Counteracts the Effect of a High-Glucose Exposure in C. elegans by Affecting the Insulin Signaling Pathway (IIS)

“…A high-glucose diet is associated with the development of metabolic diseases like obesity and type-2 diabetes, which decrease life expectancy; however, the mechanism through which a high-glucose diet (HGD) promotes these effects remains still unclear [ 55 ]. Previous studies considered HGD as a factor to develop osmotic and oxidative stress [ 56 , 57 ]. daf-16 nuclear localization depends on many factors, including the modulation of IIS, the sensory perception of stimuli by the worm, and exposure to stress among others [ 53 , 54 , 57 ].…”

Response to stress in biological disorders: Implications of stress granule assembly and function

“…Apart from heat stimuli, high concentrations of glucose have been shown to induce the assembly of RNP particles in the germline of C elegans , and further studies suggest that this process is mediated by the osmotic pressure response. They also find that destruction of RNP particle assembly is associated with reduced oocyte mass in meiotic‐block 128 . This indicates that the assembly of RNP particles in germ cells prevents mRNA degradation or early translation for maintaining oocyte quality 129,130 .…”

“…They also find that destruction of RNP particle assembly is associated with reduced oocyte mass in meiotic‐block. 128 This indicates that the assembly of RNP particles in germ cells prevents mRNA degradation or early translation for maintaining oocyte quality. 129 , 130 Reviewing how the male genital line reacts to stressors, particularly the assembly and function of SGs, could ultimately improve our understanding of human fertility and provide insights into the role of related RNP complexes in other types of cells (Figure 2 ).…”

Osmolyte accumulation regulates the SUMOylation and inclusion dynamics of the prionogenic Cyc8-Tup1 transcription corepressor

“…Hyperosmotic stress causes significant water efflux from cells, decreasing the total cellular volume and increasing macromolecular crowding [30], which has been implicated as an important factor in the condensation of protein-RNA complexes into phase separated droplets in vitro [31]. Moreover, it is well documented that hyperosmotic stress drives the formation of various cytoplasmic membraneless organelles, including stress granules in yeast and P granules in Caenorhabditis elegans [32, 33]. These dynamic bodies are primarily composed of proteins rich in low complexity sequences that are particularly enriched in polar residues such as asparagine and glutamine [34].…”

“…In accord with this model, we found that glycerol biosynthesis was a key regulator of the persistence of Cyc8 inclusions, as their lifetime was inversely correlated with cellular glycerol content after exposure to hyperosmotic stress. Compatible osmolytes have been implicated as regulators of cytoplasmic inclusions during osmotic stress in multiple organisms [32, 33]. Yeast cells accumulate glycerol following exposure to hyperosmotic stress to reestablish ionic balance, retain water, and counteract molecular crowding [35].…”