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Abstract:
Small invaginations called caveolae are present on the surface of many cells and are a form of glycosphingolipid- and cholesterol-enriched microdomains or rafts in the plasma membrane1,2. The main component of the caveolar coat is caveolin-1 (refs 3,4), a membrane protein of relative molecular mass (Mr) 21,000 (21K), which binds cholesterol5 and can form high-molecular-mass homo-oligomers resistant to sodium dodecyl sulphate (SDS)6,7. Caveolin-1 has been implicated in signal transduction, but its function remains unclear; whereas overactivation of the p42/44 MAP-kinase cascade was observed after downregulation of caveolin-1 (ref. 8), integrin-mediated activation of the Ras/extracellular-signal-regulated kinase (ERK) pathway9 or conversion of prostate cancer cells to an androgen-insensitive phenotype10 required expression of caveolin-1. To resolve the function of caveolin-1 in intact animals, we analysed caveolin-1 and glycosphingolipid/cholesterol-enriched rafts during the development of the nematode Caenorhabditis elegans. We show that C. elegans caveolin-1 (CAV-1) is expressed in the adult germ line and during embryonic development, and that CAV-1 is essential for Ras/MAP-kinase-dependent progression through the meiotic cell cycle. The function of CAV-1 is dependent on its association with cholesterol-rich membrane microdomains, providing a link between the membrane composition of germ cells and meiotic progression. Our results demonstrate that caveolin-1 and cholesterol-rich microdomains have an essential role in signal transduction in vivo and suggest a model for meiotic progression in the C. elegans germ line.
