Similarly, our findings suggest that PMK-3 stimulates GLR-1 endocytosis, perhaps via the activation of RAB-5.
These results indicate that PMK-3 and LIN-10 have opposite effects on the accumulation of GLR-1 in endosomes.
Taken together, our results suggest that PMK-3/p38 signaling regulates GLR-1 receptors by stimulating their endocytosis.
Thus, it is unlikely that PMK-3 and RPM-1 regulate GLR-1 trafficking by affecting glr-1 mRNA levels.
These results indicate that PMK-3/p38 MAPK function is required for GLR-1 accumulation in lin-10 and rpm-1 mutants.
We found that pmk-3 mutations did not enhance the phenotype of unc-11 mutations (data not shown), suggesting that mutations in unc-11 can occlude the effect of mutations in pmk-3.
Our results indicate that PMK-3 levels are not limiting for GLR-1 localization; rather, the levels of the upstream MAPKKK DLK-1 appear to dictate PMK-3/p38 MAPK activity in controlling GLR-1 trafficking.
We do not believe that pmk-3 regulates kri-1 because kri-1 transcript levels and protein localization remained unchanged in pmk-3 lf) pmk-3 lf
As G6PD knockdown cannot further decrease egg production in pmk-1 mutant, this indicates that pmk-1 may act downstream of g6pd in the same pathway for maintaining normal egg production.
Our results showed that pmk-1 mutant exhibited minor decrease of egg production compared to mock (91% of mock, P<0.001, n=70), whereas the egg production of the pmk-1/ g6pdouble) double mutant was similar to that of Gi C. elegans (P=0.136, n=70).
To further strengthen the DLK-1 section, we have added Figure 7 figure supplement 1, which shows that pmk-3, like dlk-1, suppresses two of the defects observed in the ptrn-1 mutant – the incomplete PLM commissure formation and the loss of synaptic vesicles from the synaptic patch.
