SPELL - Nematode

Citation	Ji YJ, Ugolino J, Zhang T, Lu J, Kim D, Wang J. C9orf72/ALFA-1 controls TFEB/HLH-30-dependent metabolism through dynamic regulation ofrag GTPases. PLoS Genet, 2020.
PubMed ID	32282804
Short Description	C9orf72/ALFA-1 controls TFEB/HLH-30-dependent metabolism through dynamic regulation ofrag GTPases. GEO Record: GSE137355 Platform: GPL19230 Download gene-centric, log2 transformed data: WBPaper00059541.ce.mr.csv
# of Conditions	16
Full Description	Nutrient utilization and energy metabolism are critical for the maintenance of cellular homeostasis. A mutation in the C9orf72 gene has been linked to the most common forms of neurodegenerative diseases that include amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Here we have identified an evolutionarily conserved function of C9orf72 in the regulation of the transcription factor EB (TFEB), a master regulator of autophagic and lysosomal genes that is negatively modulated by mTORC1. Loss of the C. elegans orthologue of C9orf72, ALFA-1, causes the nuclear translocation of HLH-30/TFEB, leading to activation of lipolysis and premature lethality during starvation-induced developmental arrest in C. elegans. A similar conserved pathway exists in human cells, in which C9orf72 regulates mTOR and TFEB signaling. C9orf72 interacts with and dynamically regulates the level of Rag GTPases, which are responsible for the recruitment of mTOR and TFEB on the lysosome upon amino acid signals. These results have revealed previously unknown functions of C9orf72 in nutrient sensing and metabolic pathways and suggest that dysregulation of C9orf72 functions could compromise cellular fitness under conditions of nutrient stress. Experimental Details: WBPaper00059541:N2_control_rep1 WBPaper00059541:N2_control_rep2 WBPaper00059541:N2_control_rep3 WBPaper00059541:N2_control_rep4 WBPaper00059541:N2_starvation_rep1 WBPaper00059541:N2_starvation_rep2 WBPaper00059541:N2_starvation_rep3 WBPaper00059541:N2_starvation_rep4 WBPaper00059541:alfa-1(ok3062)_control_rep1 WBPaper00059541:alfa-1(ok3062)_control_rep2 WBPaper00059541:alfa-1(ok3062)_control_rep3 WBPaper00059541:alfa-1(ok3062)_control_rep4 WBPaper00059541:alfa-1(ok3062)_starvation_rep1 WBPaper00059541:alfa-1(ok3062)_starvation_rep2 WBPaper00059541:alfa-1(ok3062)_starvation_rep3 WBPaper00059541:alfa-1(ok3062)_starvation_rep4.
Tags	Method: microarray, Species: Caenorhabditis elegans, Topic: WT vs. mutant