TRP Channels Control Serotonin Synthesis

Science's STKE  23 Mar 2004:
Vol. 2004, Issue 225, pp. tw108-TW108
DOI: 10.1126/stke.2252004TW108

The neurotransmitter serotonin (5HT) is produced in certain neurons of vertebrates and invertebrates in response to a variety of sensory stimuli, but a longstanding question has been how serotonergic neurons transduce these stimuli into intracellular signals that induce 5HT neurotransmission. Zhang et al. report that in the worm C. elegans, two Ca2+ ion channels at the surface of specific ADF-type chemosensory neurons regulate the synthesis of 5HT. Worms with loss-of-function mutations in either of two transient receptor potential V (TRPV) ion channels displayed decreased expression of tryptophan hydroxylase (TPH), a key enzyme in 5HT biosynthesis. TRPV channels are only expressed in the ADF neurons. Other genes involved in 5HT synthesis or neurotransmission were unaffected by the TRPV mutations, which indicates that TPH expression is the major target of TRPV channel signaling in these neurons. A gain-of-function mutant in the Ca2+-sensitive enzyme Ca2+/calmodulin-dependent protein kinase II (CaMKII) partially rescued TPH expression in the TRPV mutants, which suggests that it acts downstream of the ion channels to control 5HT production. The authors propose that sensory input signals that alter Ca2+ influx through the TRPV channels could control CaMKII activity, thereby affecting a downstream signaling cascade to control TPH expression and 5HT production.

S. Zhang, I. Sokolchik, G. Blanco, J. Y. Sze, Caenorhabditis elegans TRPV channel regulates 5HT biosynthesis in chemosensory neurons. Development 131, 1629-1638 (2004). [Abstract] [Full Text]