The rhythmic defecation behavior in C. elegans occurs with a period of 50 seconds and is controlled by oscillatory calcium signaling in the intestine. The first step of the digestive motor program, the posterior body wall muscle contraction, occurs without neuronal input. Instead, protons released from the intestine act as fast transmitters to elicit this contraction1,2. Protons are transported from the intestine into the pseudocoloemic space via the sodium-proton exchanger, PBO-4 (also called NHX-7). A drop in pseudocoloemic pH is thought to activate proton-gated ion channels (PBO-5 and 6) located on the posterior body wall muscles, resulting in their contraction. PBO-4 activity is precisely timed, but the mechanism underlying its activation is unclear. The
pbo-4 gene product, like its vertebrate counterparts, contains a large intracellular C-terminal tail with many binding sites for calcium-responsive proteins such as calmodulin, calmodulin kinase II, and calcineurin homologous protein. Any or all of these regulatory molecules may link calcium signaling to PBO-4 activity. The mutation of a calcineurin homologous protein (
chp-1), a co-factor for sodium-proton exchangers3, results in a posterior body contraction mutant,
pbo-1.
pbo-1(
sa7) mutants exhibit severe constipation, drastic reduction in posterior body contraction strength, low brood size and slow growth. SNP mapping and RNAi phenocopy both implicate Y71H2AL.1 as the gene mutated in
pbo-1(
sa7)III. Y71H2AL.1 encodes
chp-1, a calcium responsive protein containing two EF-hand calcium binding motifs.
pbo-1(
sa7) is a non-conservative point mutation of a calcium-coordination residue in the first EF-hand. The recently isolated allele,
pbo-1(
tm3716), eliminates the second EF-hand (provided by the National Bioresource Council). A
pbo-1 transcriptional reporter exhibits intestinal expression, positioning
pbo-1/chp-1 to respond to the intestinal calcium wave.
pbo-1/chp-1 is an excellent candidate for the molecule that coordinates the cyclic intestinal calcium wave and the initiation of posterior body contraction. Ref.: 1. Beg et al., (2008) Cell 132:149-60. 2. Pfeiffer et al., (2008) Current Bio. 18:297-302. 3. Malo and Fleigel, (2006) Can. J. Physio. Pharm. 84:1081-95.