Deformation of caveolae impacts global transcription and translation processes through relocalization of cavin-1.

ABSTRACT

Caveolae are invaginated membrane domains that provide mechanical strength to cells in addition to being focal points for the localization of signaling molecules. Caveolae are formed through the aggregation of caveolin-1 or -3 (Cav1/3), membrane proteins that assemble into multifunctional complexes with the help of caveola-associated protein cavin-1. In addition to its role in the formation of caveolae, cavin-1, also called polymerase I and transcript release factor, is further known to promote ribosomal RNA transcription in the nucleus. However, the mechanistic link between these functions is not clear. Here, we found that deforming caveolae by subjecting cells to mild osmotic stress (150-300 mOsm) changes levels of GAPDH, Hsp90, and Ras only when Cav1/cavin-1 levels are reduced, suggesting a link between caveola deformation and global protein expression. We show that this link may be due to relocalization of cavin-1 to the nucleus upon caveola deformation. Cavin-1 relocalization is also seen when Cav1-Gαq contacts change upon stimulation. Furthermore, Cav1 and cavin-1 levels have been shown to have profound effects on cytosolic RNA levels, which in turn impact the ability of cells to form stress granules and RNA-processing bodies (p-bodies) which sequester and degrade mRNAs, respectively. Our studies here using a cavin-1-knockout cell line indicate adaptive changes in cytosolic RNA levels but a reduced ability to form stress granules. Taken together, our findings suggest that caveolae, through release of cavin-1, communicate extracellular cues to the cell interior to impact transcriptional and translational.