TRPC (TRP-Canonical) channels are the founding members of the TRP superfamily, a diverse family of cation channels conserved from nematodes to humans. Most characterization of TRPC channels thus far has focused on their in vitro activities in heterologous systems; however very little is known of their functions in vitro. Understanding the biological functions and regulatory mechanisms of TRPC channels is of fundamental importance to general calcium signaling because these channels are expressed in nearly every cell type in mammals and are thought to mediate calcium entry in both excitable and nonexcitable cells. We have begun to use C. elegans as a system to study the function and regulation of TRPC channels. The C. elegans genome encodes three TRPC homologues, which we refer to as
trp-1,
trp-2 and
trp-3 [formerly CeSTRPC1, CeSTRPC2 and CeSTRPC3, Harteneck et al. (2000) Trend Neurosci 23, 159-166]. We have isolated deletion mutants in all the three worm TRPC genes, each with multiple independent alleles.
trp-3 is enriched in the sperm and is required for normal fertility.
trp-3 mutant sperm are morphologically normal and motile, but cannot fertilize oocytes after gamete contact, indicating that
trp-3 is required for fertilization. In contrast,
trp-1 and
trp-2 are expressed in excitable cells. Consistent with their expression patterns, mutations in
trp-1 and
trp-2 cause behavioral defects. Thus, activation of TRPC channels in different cell types may lead to distinct physiological outputs.