Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=18585358
&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215
Activation of pheromone-sensitive neurons is mediated by conformational
activation of pheromone-binding protein
#MMPMID18585358
Laughlin JD
; Ha TS
; Jones DNM
; Smith DP
Cell
2008[Jun]; 133
(7
): 1255-1265
PMID18585358
show ga
Detection of volatile odorants by olfactory neurons is thought to result from
direct activation of seven-transmembrane odorant receptors by odor molecules.
Here, we show that detection of the Drosophila pheromone, 11-cis vaccenyl acetate
(cVA), is instead mediated by pheromone-induced conformational shifts in the
extracellular pheromone-binding protein, LUSH. We show that LUSH undergoes a
pheromone-specific conformational change that triggers the firing of
pheromone-sensitive neurons. Amino acid substitutions in LUSH that are predicted
to reduce or enhance the conformational shift alter sensitivity to cVA as
predicted in vivo. One substitution, LUSH(D118A), produces a dominant-active LUSH
protein that stimulates T1 neurons through the neuronal receptor components Or67d
and SNMP in the complete absence of pheromone. Structural analysis of LUSH(D118A)
reveals that it closely resembles cVA-bound LUSH. Therefore, the
pheromone-binding protein is an inactive, extracellular ligand converted by
pheromone molecules into an activator of pheromone-sensitive neurons and reveals
a distinct paradigm for detection of odorants.
free
free
free
