RT Journal Article
SR Electronic
T1 Progressive Degeneration of Dopaminergic Neurons through TRP Channel-Induced Cell Death
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 5738
OP 5746
DO 10.1523/JNEUROSCI.4540-13.2014
VO 34
IS 17
A1 Nagarajan, Archana
A1 Ning, Ye
A1 Reisner, Kaja
A1 Buraei, Zafir
A1 Larsen, Jan Petter
A1 Hobert, Oliver
A1 Doitsidou, Maria
YR 2014
UL http://www.jneurosci.org/content/34/17/5738.abstract
AB Progressive neurodegenerative diseases are among the most frequently occurring aging-associated human pathologies. In a screen for Caenorhabditis elegans mutant animals that lack their normal complement of dopaminergic neurons, we identified two strains with progressive loss of dopaminergic neurons during postembryonic life. Through whole-genome sequencing we show that both strains harbor dominant (d), gain-of-function mutations in the Transient Receptor Potential (TRP) mechanosensory channel trp-4, a member of the invertebrate and vertebrate TRPN-type of the TRP family channels. Gain-of-function mutations in TRP channels have not been previously implicated in dopaminergic neuronal degeneration. We show that trp-4(d) induces cell death in dopamine neurons through a defined, calcium-related downstream pathway.