Deciphering caveolar functions by syndapin III KO-mediated impairment of caveolar invagination
Deciphering caveolar functions by syndapin III KO-mediated impairment of caveolar invagination
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DOI：
10.7554/elife.29854
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发表时间：
2017-12-05
期刊：
影响因子：
7.7
通讯作者：
Qualmann, Britta
中科院分区：
文献类型：
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作者：
Seemann, Eric;Sun, Minxuan;Qualmann, Britta
几种人类疾病都与小窝的缺乏有关。然而，小窝的功能和形成它们的关键分子机制仍然存在争议。我们发现，syndapin 111 KO小鼠的肌肉细胞显示出严重的小窝减少，让人想起人类小窝病。然而，与其他小鼠模型不同，质膜相关的小窝外壳蛋白caveolin 3和cavin 1的水平在syndapin 111 KO后均未降低。这允许将真正的小窝功能与仅由小窝蛋白存在支持的功能分开，并且还证明小窝蛋白3或小窝蛋白3和小窝蛋白1都不足以形成小窝。膜成形蛋白syndapin III对小窝内陷至关重要，KO使细胞对膜张力敏感。与小窝在平衡膜张力中的这种生理作用一致，syndapin III KO骨骼肌在体育锻炼时显示出病理学参数，这些参数也在CAVEOLIN 3突变相关的肌肉疾病中发现。
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 111 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 cavinl were both not reduced upon syndapin 111 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 cavinl are sufficient to form caveolae. The membrane-shaping protein syndapin Ill 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 Ill KO skeletal muscles showed pathological parameters upon physical exercise that are also found in CAVEOLIN3 mutation-associated muscle diseases.