The TRPC2 ion channel and pheromone sensing in the accessory olfactory system

The mammalian vomeronasal organ (VNO) has emerged as an excellent model to investigate the signaling mechanisms, mode of activation, biological function, and molecular evolution of transient receptor potential (TRP) channels in real neurons and real physiological systems. TRPC2, a member of the canonical TRPC subfamily, is highly localized to the dendritic tip of vomeronasal sensory neurons. Targeted deletion of the TRPC2 gene has established that TRPC2 plays a fundamental role in the detection of pheromonal signals by the VNO. TRPC2-deficient mice exhibit striking behavioral defects in the regulation of sexual and social behaviors. A novel Ca(2+)-permeable, diacylglycerol-activated cation channel found at the dendritic tip of vomeronasal neurons is severely defective in TRPC2 mutants, providing the first clear example of native diacylglycerol-gated cation channels in the mammalian nervous system. The TRPC2 gene has become an important marker for the evolution of VNO-dependent pheromone signaling in primates.