TRPC channels modulate locomotive behavior of C. elegans

Abstract

Locomotion is mediated by coordinated processes between sensory and motor system in animals. C. elegansgenerates sinusoidal locomotion via periodic bending of its head and body. The putative proprioceptive SMD motor neurons, that innervate to head muscles and project posterior processes to the tail, have been proposed to sense the body stretch and regulate head locomotion (White et al., 1986; Hendricks et al., 2012; Shen et al., 2016). However, the molecular mechanisms by which SMD regulates head movementare still unclear. To identify factors that mediate SMD-mediated head bending, we performed candidate gene search and found that TRPC channels, trp-1and trp-2, are co-expressed in SMD (Feng et al., 2006). Since we did not observed altered locomotion defects in single mutants of either trp-1 or trp-2, we next generated trp-1 trp-2doublemutants and found that these animals exhibit ventral-directed circles during forward movement; we name this phenotype as ventralcircling. Expression of either TRP-1 or TRP-2 by using a SMDD specific promoter rescued ventral circling phenotype of trp-1 trp-2mutants, and SMDD axonal morphological defect mutants also showed the ventral circling. These results indicate that the ventralcircling phenotype of trp-1 trp-2 mutants is due to the functional defects of SMDD. Ca2+activity of SMD is correlated with head bending direction in wild-type animals, whereas Ca2+activity SMDD but not SMDV is not correlated with head bending in trp-1 trp-2 mutants. These impaired correlation Ca2+dynamic of SMDD with head bending in trp-1 trp-2double mutants was restored by expressing trp-1cDNA using the SMDD specific promoter. Furthermore, ectopic expression of the known stretch receptors, C. elegans trp-4 orDrosophila TRPγ in SMDD were sufficient to rescue ventral circling locomotion of trp-1 trp-2 double mutants. Currently, we are investigating stretch-activation of TRP-1 or TRP-2 by performing electrophysiology in heterologous systems. Taken together, we propose that trp-1and trp-2act as stretch receptors in the SMD motor neurons to sense the dorsal head movement and to correlate SMDD motor neuronal activity with head bending