TY  - GEN
T1  - Overactive EGF signaling promotes uv1 cell survival via increased phosphatidylcholine levels and suppression of SBP-1
AU  - Crook, Matt
AU  - Hanna-Rose, Wendy
DO  - 10.17912/micropub.biology.000266
UR  - http://beta.micropublication.org/journals/biology/micropub-biology-000266/
AB  - Caenorhabditis elegans uv1 cells undergo a dramatic cell death in a pnc-1 NAD+ salvage deficient mutant (Huang and Hanna-Rose, 2006). uv1 cell death is a result of accumulation of the PNC-1 substrate nicotinamide (NAM), which overactivates the OCR-4 OSM-9 transient receptor potential cation V (TRPV) channel, causing excitotoxicity (Upadhyay, et al., 2016, Vrablik, et al., 2009). Reduced uv1 cell survival is almost completely restored in pnc-1 mutant animals by sustained activation of the Epidermal Growth Factor (EGF) receptor LET-23, either by overexpression of the ligand LIN-3 or by a gain of function mutation in the receptor (Huang and Hanna-Rose, 2006). We presume that the constitutively activated receptor acts cell autonomously in the uv1 cells to promote survival, but have no direct evidence in support of that presumption, besides a prior report showing that a let-23(sa62) gain of function allele was able to induce uv1 specification in the absence of LIN-3 (Chang, et al., 1999). To find genes required for uv1 survival in a let-23(sa62gf); pnc-1(pk9605) background, we performed an RNAi screen and found that phosphatidylcholine synthesis via PMT-1 or PCYT-1 is required for LET-23 to promote uv1 cell survival in pnc-1 background (Crook, et al., 2016). Moreover, treatment with exogenous phosphatidylcholine alone is partially sufficient to promote cell survival in the pnc-1 mutant (Crook, et al., 2016). The requirement of phosphatidylcholine synthesis indicates that membrane phospholipid composition, and by extension disruption of lipid homeostasis, may play a role in preventing TRPV-induced excitotoxic death.
PY  - 2020
JO  - microPublication Biology
ER  -