Stress induced nuclear granules form in response to accumulation of misfolded proteins in Caenorhabditis elegans.
BACKGROUND
Environmental stress can affect the viability or fecundity of an organism. Environmental stressors may affect the genome or the proteome and can cause cellular distress by contributing to protein damage or misfolding. This study examines the cellular response to environmental stress in the germline of the nematode, C. elegans.


RESULTS
Salt stress, oxidative stress, and starvation, but not heat shock, induce the relocalization of ubiquitin, proteasome, and the TIAR-2 protein into distinct subnuclear regions referred to as stress induced nuclear granules (SINGs). The SINGs form within 1 h of stress initiation and do not require intertissue signaling. K48-linked polyubiquitin chains but not K63 chains are enriched in SINGs. Worms with a mutation in the conjugating enzyme, ubc-18, do not form SINGs. Additionally, knockdown of ubc-20 and ubc-22 reduces the level of SING formation as does knockdown of the ubiquitin ligase chn-1, a CHIP homolog. The nuclear import machinery is required for SING formation. Stressed embryos containing SINGs fail to hatch and cell division in these embryos is halted. The formation of SINGs can be prevented by pre-exposure to a brief period of heat shock before stress exposure. Heat shock inhibition of SINGs is dependent upon the HSF-1 transcription factor.


CONCLUSIONS
The heat shock results suggest that chaperone expression can prevent SING formation and that the accumulation of damaged or misfolded proteins is a necessary precursor to SING formation. Thus, SINGs may be part of a novel protein quality control system. The data suggest an interesting model where SINGs represent sites of localized protein degradation for nuclear or cytosolic proteins. Thus, the physiological impacts of environmental stress may begin at the cellular level with the formation of stress induced nuclear granules.
['Sampuda|Katherine M|KM|', 'Riley|Mason|M|', 'Boyd|Lynn|L|0000-0003-4818-1157']
D021581:Active Transport, Cell Nucleus D000818:Animals D017173:Caenorhabditis elegans D029742:Caenorhabditis elegans Proteins D002455:Cell Division D002467:Cell Nucleus D003594:Cytoplasmic Granules D004625:Embryo, Nonmammalian D049452:Green Fluorescent Proteins D007422:Intestines D008239:Lysine D008954:Models, Biological D018384:Oxidative Stress D025821:Polyubiquitin D046988:Proteasome Endopeptidase Complex D017510:Protein Folding D012965:Sodium Chloride D013312:Stress, Physiological D054875:Ubiquitination
Salt stress Oxidative stress Starvation Ubiquitin Proteasome Nuclear body