Worm Breeder's Gazette 13(5): 53 (February 1, 1995)

These abstracts should not be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.

vab-8 May Encode a Protein with Kex2 Cleavage Sites.

Ming-shiu Hung, 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