Role of p11 in cellular and behavioral effects of 5-HT4 receptor stimulation.
p11 (S100A10), a member of a large family of S100 proteins, interacts with serotonin receptor 1B (5-HTR1B), modulates 5-HT1B receptor signal transduction, and is required for antidepressant responses to activation of this receptor. In the current study, we investigated the specificity of the interaction between 5-HTR1B and p11 by screening brain-expressed S100 proteins against serotonin and noradrenergic receptors. The data indicate that p11 is unique among its family members for its interactions with defined serotonin receptors. We identify a novel p11-interacting receptor (5-HTR4) and characterize the interaction between p11 and 5-HTR4, demonstrating that (1) p11 and 5-HTR4 mRNA and protein are coexpressed in brain regions that are relevant for major depression, (2) p11 increases 5-HTR4 surface expression and facilitates 5-HTR4 signaling, and (3) p11 is required for the behavioral antidepressant responses to 5-HTR4 stimulation in vivo. The essential role played by p11 in modulating signaling through 5-HT4 as well as 5-HT1B receptors supports the concept that this protein may be a key determinant of vulnerability to depression.
Warner-Schmidt
Jennifer L
JL
Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, New York 10065, USA.
Flajolet
Marc
M
Maller
Abigail
A
Chen
Emily Y
EY
Qi
Hongshi
H
Svenningsson
Per
P
Greengard
Paul
P
D000818:Animals; D017306:Annexin A2 / Q000502:physiology*; D017209:Apoptosis / Q000502:physiology*; D019556:COS Cells; D002462:Cell Membrane / Q000502:physiology*; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D003866:Depressive Disorder / Q000378:metabolism; D005106:Exploratory Behavior / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011985:Receptors, Serotonin / Q000502:physiology*; D044422:Receptors, Serotonin, 5-HT4 / Q000502:physiology*; D009418:S100 Proteins / Q000502:physiology*; D000099248:S100 Calcium Binding Protein A10
D017306:Annexin A2; D011985:Receptors, Serotonin; D044422:Receptors, Serotonin, 5-HT4; D009418:S100 Proteins; D000099248:S100 Calcium Binding Protein A10; C078730:serotonin 5 receptor