Differential addressing of 5-HT1A and 5-HT1B receptors in epithelial cellsand neurons

The 5-HT1A and 5-HT1B serotonin receptors are expressed in a variety of neu rons in the central nervous system. While the 5-HT1A receptor is found on s omas and dendrites, the 5-HT1B receptor has been suggested to be localized predominantly on axon terminals. To study the intracellular addressing of t hese receptors, we have used in vitro systems including Madin-Darby canine kidney (MDCK II) epithelial cells and primary neuronal cultures, Furthermor e, we have extended these studies to examine addressing in vivo in transgen ic mice. In epithelial cells, 5-HT1A receptors are found on both apical and basolateral membranes while 5-HT1B receptors are found exclusively in intr acellular vesicles. In hippocampal neuronal cultures, 5-HT1A receptors are expressed on somatodendritic membranes but are absent from axons, In contra st, 5-HT1B receptors are found on both dendritic and axonal membranes, incl uding growth cones where they accumulate. Using 5-HT1A and 5-HT1B knockout mice and the binary tTA/tetO system, we generated mice expressing these rec eptors in striatal neurons. These in vivo experiments demonstrate that, in striatal medium spiny neurons, the 5-HT1A receptor is restricted to the som atodendritic level, while 5-HT1B receptors are shipped exclusively toward a xon terminals. Therefore, in all systems we have examined, there is a diffe rential sorting of the 5-HT1A and 5-HT1B receptors, Furthermore, we conclud e that our in vivo transgenic system is the only model that reconstitutes p roper sorting pf these receptors.