Project description:This SuperSeries is composed of the following subset Series: GSE24749: Rap1a GTPase mVSM Knockout vs. Rescue miRNA Expression GSE25702: Rap1a GTPase mVSM Knockout vs. Rescue mRNA Expression Refer to individual Series
Project description:miRNA profiling of mouse tail artery explanted microvascular smooth muscle (mVSM) cells comparing Rap1a -/- mVSM cells trasduced with vector backbone (control) with Rap1a -/- mVSM cells transduced with a Rap1 CA 'rescue' plasmid. The experiment will compare miRNA expression in Rap1A -/- mVSMs and 'rescued'with Rap1A CA.
Project description:Transcriptional profiling of mouse tail artery explanted microvascular smooth muscle (mVSM) cells comparing Rap1a -/- mVSM cells transduced with vector backbone (control) with Rap1a -/- mVSM cells transduced with a Rap1 CA 'rescue' plasmid. The experiment will compare mRNA expression in Rap1A -/- mVSMs and 'rescued'with Rap1A CA.
Project description:Autophagy is a lysosomal degradation pathway that mediates protein and organelle turnover and maintains cellular homeostasis. Autophagosomes transport cargo to lysosomes and their formation is dependent on an appropriate lipid supply. Here, we show that the knockout of the RAB GTPase RAB18 interferes with lipid droplet (LD) metabolism, resulting in an impaired fatty acid mobilization. The reduced LD-derived lipid availability influences autophagy and provokes adaptive modifications of the autophagy network, which include increased ATG2B expression and ATG12-ATG5 conjugate formation as well as enhanced ATG2B and ATG9A phosphorylation. Phosphorylation of ATG9A directs this transmembrane protein to the site of autophagosome formation and this particular modification is sufficient to rescue autophagic activity under basal conditions in the absence of RAB18. However, it is incapable of enabling an increased autophagy under inductive conditions. Thus, we illustrate the role of RAB18 in connecting LDs and autophagy, further emphasize the importance of LD-derived lipids for the degradative pathway, and characterize an ATG9A phosphorylation-dependent autophagy rescue mechanism as an adaptive response that maintains autophagy under conditions of reduced LD-derived lipid availability.