A team of biologists from Institut Curie’s Research Center is making discoveries on the normal functioning and the pathological malfunctions of caveolae, cellular structures with a number of implications.
Discovered in the 1950s, caveolae are small structures that form invaginations in cell membranes, and their function has long been a mystery. It was not until 2011 that biologists and physicists from Institut Curie uncovered their role, findings that were published in the journal Cell (1). These rafts of folds and back-folds are designed to absorb the mechanical impacts that cells are subject to; they fold and unfold like an accordion, so that the cell walls can bend without breaking.
Today, the same team, in collaboration with the Institut de myologie, has revealed new findings in the journal Nature Communications (2). Christophe Lamaze, head of the Membrane dynamics and mechanics of intracellular signaling team (Cellular and Chemical Biology Unit, CNRS / Inserm / Institut Curie and affiliated to the LabEx CelTisPhyBio and PSL), Mélissa Dewulf and Cedric Blouin, researchers in his team, studied the muscle cells of patients suffering from a myopathy in which the caveolin-3 gene, a muscle-specific caveolae, is muted. The result is that these cells are not very resistant to mechanical stress. But, more surprisingly, they found that caveolae play a role in the transmission of certain messages inside cells. Specifically, they found that in diseased cells, the response to interleukin-6, an inflammation molecule, was permanently activated, whereas in normal conditions this response is regulated by the caveolae. They have also discovered similar mechanisms in breast cancer cells that will be published soon. Notably, last year in the Journal of Cell Biology (3), they had shown that some components of the caveolae play a role in breast cancer cell invasion.
And from May 12 to 16 in La Baule, France, our caveolae specialists will bring together around one hundred researchers from around the world (including Europe, the United States, Chile, Japan and Australia) to discuss this burgeoning topic as part of a meeting sponsored by the European Molecular Biology Organization (EMBO), an association of Europe’s best researchers in life sciences.
- Cells respond to mechanical stress by rapid disassembly of caveolae. Sinha B, Köster D, Ruez R, Gonnord P, Bastiani M, Abankwa D, Stan RV, Butler-Browne G, Vedie B, Johannes L, Morone N, Parton RG, Raposo G, Sens P, Lamaze C, Nassoy P. 2011 Feb 4;144(3):402-13. doi: 10.1016/j.cell.2010.12.031. PMID: 21295700
- Dystrophy-associated caveolin-3 mutations reveal that caveolae couple IL6/STAT3 signaling with mechanosensing in human muscle cells. Dewulf M, Köster D, Sinha B, Viaris de Lesegno C, Chambon V, Bigot A, Bensalah M, Negroni E, Tardif T, Podkalicka J, Johannes L, Nassoy P, Butler-Browne G, Lamaze C and Blouin CM. Nat Comm. 2019
- EHD2 is a mechanotransducer connecting caveolae dynamics with gene transcription. Torrino S, Shen WW, Blouin CM, Mani SK, Viaris de Lesegno C, Bost P, Grassart A, Köster D, Valades-Cruz CA, Chambon V, Johannes L, Pierobon P, Soumelis V, Coirault C, Vassilopoulos S, Lamaze C. J Cell Biol. 2018 Dec 3;217(12):4092-4105. doi: 10.1083/jcb.201801122. Epub 2018 Oct 22 PMID: 30348749