vab-8 may encode a protein with Kex2 cleavage sites Ming-shiu Hung and Jeff Way. Dept. of Biology, Nelson Labs, Rutgers University, Piscataway NJ 08855. We have identified and sequenced a ~5kb DNA fragment that rescues the withered tail phenotype of
vab-8(
e1017), and isolated some corresponding, incomplete cDNAs.
vab-8 is adjacent to
myo-3 and these two genes are transcribed towards each other. Our current interpretation of the sequence suggests that the
vab-8 protein is 571 amino acids and contains 20 sites where two or three arginine and/or lysine residues are adjacent. Such pairs of basic amino acids are the target for the Kex2 protease, which is located in the Golgi and which cleaves secreted proteins. In addition, there may be a 18 aa hydrophobic stretch at the N-terminus, followed by a His-Lys sequence that also might be a cleavage site. The C terminal 300 amino acids are confirmed by our cDNAs, but the putative N-terminus has been identified only by sequence-gazing and still needs to be confirmed.
vab-8 mutants show a withered tail phenotype as a result of a failure of the posterior migration of the CAN neuron. In addition, some alleles cause an anterior over-migration of the HSN cell (Manser and Wood, Devel. Genetics 11: 49-64). At a low frequency, extra
mec-3-expressing PLM cells are observed (Way et al., Dev. Dynamics 194: 289-302), which could be due to a failure in sensing the anterior-posterior direction leading to an asymmetric cell division defect. Bruce Wightman and Gian Garriga (personal communication) have also shown that
vab-8 is allelic to
unc-107, which has an axon guidance defect, and that the extension of many axons is defective
vab-8(-). Only events in the anterior-posterior direction are affected in this mutant. Thus,
vab-8 may be part of a directional information system that would be complementary to the
unc-5/unc-6 system for the dorsal-ventral direction.