The production of the second messenger inositol 1,4,5-trisphosphate (IP3) through the hydrolysis of PIP2 is a key mechanism by which cell surface stimuli can regulate intracellular calcium levels. It has been shown that, in the model organism Caenorhabditis elegans, the IP3 receptor (IP3R) is widely expressed and is involved in the regulation of a wide range of developmental and physiological processes (1). Previous work has shown that calcium signals are associated with caveolae (2) and that the components of IP3 signalling are also localised within caveolae (3). We therefore set out to establish whether caveolae or lipid rafts play a role in the modulation of IP3 and calcium-mediated signalling in C. elegans. There are two caveolin genes in C.elegans (4) of which
cav-1 has been implicated in the regulation of meiotic cell progression (5). To establish the expression pattern of both caveolins we have made transgenic animals carrying the
cav-1 and
cav-2 genes fused to gfp.
cav-1 is widely expressed in embryos and the nervous system, while
cav-2 is only expressed in gut cells. Interestingly, no co-localisation occurs. To test the role of
cav-1 and
cav-2 in IP3-mediated processes we are examining the effects of knocking down caveolins using RNA-mediated interference (RNAi) and gene knock-outs. Furthermore, overexpression of caveolins have revealed interesting phenotypes. 1.Walker DS, Gower NJ, Ly S, Bradley GL, Baylis HA (2002) Mol Biol Cell 13, 1329-37. 2.Isshiki M, Ando J, Yamamoto K, Fujita T, Ying Y, Anderson RG (2002) J Cell Sci 115, 475-84. 3.Isshiki M, Anderson, RG (1999) Cell Calcium 26, 201-8. 4.Tang Z, Okamoto T, Boontrakulpoontawee P, Katada T, Otsuka AJ, Lisanti MP (1997) J Biol Chem 272, 2437-45. 5.Scheel J, Srinivasan J, Honnert U, Henske A, Kurzchalia TV (1999) Nat Cell Biol 1, 127-9.