Sensory Perception

DAG, a Social Signal

Science's STKE  04 Nov 2003:
Vol. 2003, Issue 207, pp. tw427-TW427
DOI: 10.1126/stke.2003.207.tw427

In some mammals, pheromones (a special type of odorant signal) detected by the vomeronasal organ (VNO) are major controllers of social behaviors, such as aggression and mate choice. Although it is known that the transient receptor potential channel TRPC2 is essential for VNO function, there is considerable debate regarding the molecular signal that activates this cation channel. Lucas et al. provide evidence that TRPC2 in mice is activated by diacylglycerol (DAG) produced from phospholipase C (PLC). Patch-clamp analysis of inside-out patches from dendritic tips of freshly dissociated vomeronasal sensory neurons (VSNs) showed that application of DAG analogs [such as 1-stearoyl-2-arachidonoyl-sn-glycerol (SAG)], but not inositol trisphosphate (IP3) or calcium alone, stimulated a nonselective cationic current. Whole-cell patch clamp analysis of VSNs from wild-type or TRPC2–/– mice showed that the SAG-stimulated current was present in the wild-type preparations as long as the dendrite was intact but that there was no signal from the TRPC2–/– preparations. The SAG-stimulated current did not result from SAG feedback activation of PLC activity or stimulation of protein kinase C activity, because increased conductance was observed even in the presence of pharmacological inhibitors of these two enzymes. In VNO slice preparations, a urine-evoked current (urine is a potent source of mouse pheromones) and the SAG-evoked currents had the same electrophysiological and pharmacological properties. Finally, inhibition of DAG kinase, an enzyme that would terminate the action of DAG in stimulating the channel, produced a sustained activation of the TRPC2-dependent channel. Thus, the authors propose that activation of PLC stimulates the production of DAG, which activates the TRPC2 channel, and this activity is terminated through the metabolism of DAG by DAG kinase.

P. Lucas, K. Ukhanov, T. Leinders-Zufall, F. Zufall, A diacylglycerol-gated cation channel in vomeronasal neuron dendrites is impaired in TRPC2 mutant mice: Mechanism of pheromone transduction. Neuron 40, 551-561 (2003). [Online Journal]