TY - JOUR T1 - Role of p11 in Cellular and Behavioral Effects of 5-HT4 Receptor Stimulation JF - The Journal of Neuroscience JO - J. Neurosci. SP - 1937 LP - 1946 DO - 10.1523/JNEUROSCI.5343-08.2009 VL - 29 IS - 6 AU - Jennifer L. Warner-Schmidt AU - Marc Flajolet AU - Abigail Maller AU - Emily Y. Chen AU - Hongshi Qi AU - Per Svenningsson AU - Paul Greengard Y1 - 2009/02/11 UR - http://www.jneurosci.org/content/29/6/1937.abstract N2 - 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. ER -