TY - JOUR TI - Deciphering caveolar functions by syndapin III KO-mediated impairment of caveolar invagination AU - Seemann, Eric AU - Sun, Minxuan AU - Krueger, Sarah AU - Tröger, Jessica AU - Hou, Wenya AU - Haag, Natja AU - Schüler, Susann AU - Westermann, Martin AU - Huebner, Christian A AU - Romeike, Bernd AU - Kessels, Michael M AU - Qualmann, Britta A2 - Pfeffer, Suzanne R VL - 6 PY - 2017 DA - 2017/12/05 SP - e29854 C1 - eLife 2017;6:e29854 DO - 10.7554/eLife.29854 UR - https://doi.org/10.7554/eLife.29854 AB - Several human diseases are associated with a lack of caveolae. Yet, the functions of caveolae and the molecular mechanisms critical for shaping them still are debated. We show that muscle cells of syndapin III KO mice show severe reductions of caveolae reminiscent of human caveolinopathies. Yet, different from other mouse models, the levels of the plasma membrane-associated caveolar coat proteins caveolin3 and cavin1 were both not reduced upon syndapin III KO. This allowed for dissecting bona fide caveolar functions from those supported by mere caveolin presence and also demonstrated that neither caveolin3 nor caveolin3 and cavin1 are sufficient to form caveolae. The membrane-shaping protein syndapin III is crucial for caveolar invagination and KO rendered the cells sensitive to membrane tensions. Consistent with this physiological role of caveolae in counterpoising membrane tensions, syndapin III KO skeletal muscles showed pathological parameters upon physical exercise that are also found in CAVEOLIN3 mutation-associated muscle diseases. KW - caveolar invagination KW - nanodomains KW - ultrastructural analyses of membrane topologies KW - mechanical stress KW - caveolinopathies JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -