Differential addressing of 5-HT1A and 5-HT1B receptors in epithelial cells and neurons.
The 5-HT1A and 5-HT1B serotonin receptors are expressed in a variety of neurons in the central nervous system. While the 5-HT1A receptor is found on somas and dendrites, the 5-HT1B receptor has been suggested to be localized predominantly on axon terminals. To study the intracellular addressing of these receptors, we have used in vitro systems including Madin-Darby canine kidney (MDCK II) epithelial cells and primary neuronal cultures. Furthermore, we have extended these studies to examine addressing in vivo in transgenic mice. In epithelial cells, 5-HT1A receptors are found on both apical and basolateral membranes while 5-HT1B receptors are found exclusively in intracellular vesicles. In hippocampal neuronal cultures, 5-HT1A receptors are expressed on somatodendritic membranes but are absent from axons. In contrast, 5-HT1B receptors are found on both dendritic and axonal membranes, including growth cones where they accumulate. Using 5-HT1A and 5-HT1B knockout mice and the binary tTA/tetO system, we generated mice expressing these receptors in striatal neurons. These in vivo experiments demonstrate that, in striatal medium spiny neurons, the 5-HT1A receptor is restricted to the somatodendritic level, while 5-HT1B receptors are shipped exclusively toward axon terminals. Therefore, in all systems we have examined, there is a differential sorting of the 5-HT1A and 5-HT1B receptors. Furthermore, we conclude that our in vivo transgenic system is the only model that reconstitutes proper sorting of these receptors.
Ghavami
A
A
Center for Neurobiology and Behavior, Columbia University, New York, NY 10032, USA.
Stark
K L
KL
Jareb
M
M
Ramboz
S
S
Ségu
L
L
Hen
R
R
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000493:pharmacokinetics; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000502:physiology*; D002460:Cell Line; D002462:Cell Membrane / Q000502:physiology / Q000648:ultrastructure; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000502:physiology; D004285:Dogs; D004847:Epithelial Cells / Q000502:physiology* / Q000648:ultrastructure; D020120:Iodocyanopindolol / Q000493:pharmacokinetics; D007668:Kidney; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016253:Microscopy, Immunoelectron; D009474:Neurons / Q000502:physiology* / Q000648:ultrastructure; D011869:Radioligand Assay; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D044263:Receptors, Serotonin, 5-HT1; D011994:Recombinant Proteins / Q000096:biosynthesis; D014162:Transfection
D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D011994:Recombinant Proteins; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D020120:Iodocyanopindolol