Alterations in 5-HT1B receptor function by p11 in depression-like states.
The pathophysiology of depression remains enigmatic, although abnormalities in serotonin signaling have been implicated. We have found that the serotonin 1B receptor [5-hydroxytryptamine (5-HT1B) receptor] interacts with p11. p11 increases localization of 5-HT1B receptors at the cell surface. p11 is increased in rodent brains by antidepressants or electroconvulsive therapy, but decreased in an animal model of depression and in brain tissue from depressed patients. Overexpression of p11 increases 5-HT1B receptor function in cells and recapitulates certain behaviors seen after antidepressant treatment in mice. p11 knockout mice exhibit a depression-like phenotype and have reduced responsiveness to 5-HT1B receptor agonists and reduced behavioral reactions to an antidepressant.
Svenningsson
Per
P
Laboratory of Molecular and Cellular Neuroscience, Rockefeller University, New York, NY 10021, USA.
Chergui
Karima
K
Rachleff
Ilan
I
Flajolet
Marc
M
Zhang
Xiaoqun
X
El Yacoubi
Malika
M
Vaugeois
Jean-Marie
JM
Nomikos
George G
GG
Greengard
Paul
P
D000328:Adult; D000368:Aged; D000818:Animals; D017306:Annexin A2 / Q000235:genetics / Q000378:metabolism*; D000928:Antidepressive Agents / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D003863:Depression / Q000235:genetics / Q000378:metabolism*; D004565:Electroconvulsive Therapy; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008875:Middle Aged; D009474:Neurons / Q000378:metabolism; D051381:Rats; D044302:Receptor, Serotonin, 5-HT1B / Q000378:metabolism*; D009418:S100 Proteins / Q000235:genetics / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction; D020798:Two-Hybrid System Techniques; D000099248:S100 Calcium Binding Protein A10
D017306:Annexin A2; D000928:Antidepressive Agents; D044302:Receptor, Serotonin, 5-HT1B; D009418:S100 Proteins; D012701:Serotonin; D000099248:S100 Calcium Binding Protein A10