TTX-4, a novel PKC (nPKC)-epsilon ortholog of C. elegans, plays significant roles in signal sensation of most, if not all, of sensory neurons (see 2001 IWM and 2002 JWM abstracts). nPKC and cPKC are known to be activated by diacylglycerol (DAG) or phorbol ester such as phorbol-12-myristate-13-acetate (PMA). We recently showed that PMA only activates TTX-4 in AFD thermosensory neuron to direct thermotaxis, suggesting that TTX-4 is the most important PKC required for thermosensation. To see whether TTX-4 nPKC is activated by DAG in other neurons and/or other sensory modalities, we investigated the effect of PMA on chemotaxis to AWC-sensed odorants. PMA-treated wild type animals displayed normal responses to these odorants as non-treated wild type animals. By contrast, PMA-treated
ttx-4 mutants did show weak but noticeable olfactory responses, whereas non-treated
ttx-4 mutants remained defective. Since the weak olfactory responses observed in PMA-treated
ttx-4 mutants could be caused by PMA activation of other PKCs, we investigated olfaction of
tpa-1 mutants.
tpa-1 encodes a nPKC-delta/theta homolog (Tabuse et al., 1989 Science 243, 1713). PMA-treated
tpa-1 mutants responded quite normally to AWC-sensed odorants, while
tpa-1 mutants were slightly defective in chemotaxis to these odorants. These results led us to propose that PMA activates TPA-1 nPKC-delta/theta in
ttx-4 mutants and PMA activates TTX-4 nPKC-epsilon in
tpa-1 mutants, thereby achieving better AWC olfactory responses in both mutants when treated with PMA. Consistent with this possibility, PMA-treated
tpa-1;
ttx-4 double mutants remained defective in the olfactory responses. We obtained the similar results on chemotaxis to AWA-sensed odorants. Thus, TPA-1 nPKC-delta/theta is perhaps necessary for olfaction in addition to TTX-4 nPKC-epsilon. Diacylglycerol kinase (DGK) changes DAG to phosphatidic acid (PA) by phosphorylation and negatively regulates PKC.
dgk-1 encodes a DGK homolog (Nurrish et al., 1999 Neuron 24, 231). We recently found that
dgk-1 mutants showed cryophilic phenotype (see Ohta et al., 2002 JWM abstract).
ttx-4;
dgk-1 double mutants showed thermophilic phenotype as
ttx-4 mutants, which is consistent the model that DGK-1 functions in the upstream of TTX-4. To test this model, we are in the process of identification of neurons where DGK-1 functions.