PMID- 35513070 OWN - NLM STAT- MEDLINE DCOM- 20220629 LR - 20220716 IS - 1083-351X (Electronic) IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 298 IP - 6 DP - 2022 Jun TI - Deformation of caveolae impacts global transcription and translation processes through relocalization of cavin-1. PG - 102005 LID - S0021-9258(22)00445-8 [pii] LID - 10.1016/j.jbc.2022.102005 [doi] LID - 102005 AB - 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-Galphaq 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. CI - Copyright (c) 2022 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Qifti, Androniqi AU - Qifti A AD - Department of Chemistry and Biochemistry, Worcester Polytechnic Institute, Worcester, Massachusetts, USA. FAU - Balaji, Shravani AU - Balaji S AD - Department of Chemistry and Biochemistry, Worcester Polytechnic Institute, Worcester, Massachusetts, USA. FAU - Scarlata, Suzanne AU - Scarlata S AD - Department of Chemistry and Biochemistry, Worcester Polytechnic Institute, Worcester, Massachusetts, USA. Electronic address: sfscarlata@wpi.edu. LA - eng GR - R01 GM116178/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20220502 PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Caveolin 1) RN - 0 (Membrane Proteins) RN - 0 (RNA, Messenger) RN - 0 (RNA-Binding Proteins) SB - IM MH - *Caveolae/metabolism/pathology MH - *Caveolin 1/genetics/metabolism MH - Cell Line MH - Gene Knockout Techniques MH - Membrane Proteins/metabolism MH - *Protein Biosynthesis MH - RNA, Messenger/metabolism MH - *RNA-Binding Proteins/genetics/metabolism MH - Signal Transduction MH - *Transcription, Genetic PMC - PMC9168624 OTO - NOTNLM OT - caveola domains OT - cavin-1 OT - cell stress OT - nuclear relocalization OT - protein translation COIS- Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article. EDAT- 2022/05/06 06:00 MHDA- 2022/06/30 06:00 PMCR- 2022/05/02 CRDT- 2022/05/05 21:45 PHST- 2021/12/21 00:00 [received] PHST- 2022/04/16 00:00 [revised] PHST- 2022/04/19 00:00 [accepted] PHST- 2022/05/06 06:00 [pubmed] PHST- 2022/06/30 06:00 [medline] PHST- 2022/05/05 21:45 [entrez] PHST- 2022/05/02 00:00 [pmc-release] AID - S0021-9258(22)00445-8 [pii] AID - 102005 [pii] AID - 10.1016/j.jbc.2022.102005 [doi] PST - ppublish SO - J Biol Chem. 2022 Jun;298(6):102005. doi: 10.1016/j.jbc.2022.102005. Epub 2022 May 2.