TY  - GEN
T1  - oxi-1 and fshr-1 are required for neuromuscular signaling under normal and oxidative stress conditions in C. elegans
AU  - Wei, Barry
AU  - Kowalski, Jennifer R.
DO  - 10.17912/pfyw-ft85
UR  - http://beta.micropublication.org/journals/biology/pfyw-ft85/
AB  - Reactive oxygen species (ROS) contribute to neuronal degeneration by readily reacting with cellular components, consequently breaking down cellular integrity. Excess ROS often leads to oxidative stress, which results from destabilization of the organism’s ability to control the balance between antioxidants and free radicals (Chandra et al. 2015). The ubiquitin-proteasome system helps to regulate oxidative stress and overall damage to cellular components by forming chains of ubiquitin polypeptides on cellular proteins; these chains then serve as a signal to break down the attached protein (Hershko et al. 1983). Mutation of UBE3B, an E3 ubiquitin ligase, has been found to lead to Blepharophimosis-Ptosis-Intellectual-Disability Syndrome (BPID) in human infants, indicating potential involvement of UBE3B in the regulation of neuronal signaling in the brain (Basel-Vanagaite et al. 2012). The UBE3B protein was also shown to be involved in mitochondrial function and oxidative stress responses in mammalian cells (Braganza et al. 2017). In C. elegans, the oxi-1 gene encodes an ubiquitin ligase homologous to UBE3B (58% amino acid similarity); expression of C. elegans oxi-1 is induced by oxidative stress and is required for proteasomal responses to this stress (Basel-Vanagaite et al. 2012). However, despite the link to neurodevelopmental disorders including BPID, specific roles for UBE3B or oxi-1 in neuronal biology and synaptic function, with or without oxidative stress, have not been explored (Basel-Vanagaite et al. 2012). A second C. elegans gene fshr-1, which encodes a G protein-coupled receptor homologous to a family of mammalian glycopeptide hormone receptors (Cho et al, 2007), is also involved in both oxidative stress responses and neuronal signaling. Specifically, fshr-1 regulates expression of gcs-1, an oxidative-stress response gene (Miller et al. 2015) and was identified in an RNAi interference screen as a gene required for proper structure and function of neuromuscular synapses (Sieburth et al. 2005). Despite data suggesting roles for oxi-1 UBE3B, and fshr-1 in neuronal signaling, which is susceptible to oxidative damage, neither gene has been investigated with regards to neuronal signaling in the presence of oxidative stress. Here, we tested the requirements of both oxi-1 and fshr-1 for their effects on neuromuscular signaling under both normal and oxidative stress conditions in C. elegans.  
PY  - 2018
JO  - microPublication Biology
ER  -