title: Differential expression of neuronal dopamine and serotonin transporters DAT and SERT in megakaryocytes and platelets generated from human MEG-01 megakaryoblasts.
abstract: In the central nervous system, serotonergic and dopaminergic signaling is terminated by the activity of specialized transporter proteins for serotonin (SERT) and dopamine (DAT). These transporter proteins are found both on the cell surface and in intracellular transport vesicles. Trafficking between these subcellular domains regulates the efficiency of removal of extracellular neurotransmitters and hence the efficacy of neuronal signaling. Therefore, it is of high interest to gain more insight into the regulatory mechanisms of the human DAT and SERT cell surface expression in their natural surroundings, i.e., in human cells. Because it is not possible to cultivate human neuronal cells expressing these transporter proteins, there is a need to find other human cells expressing these neuronal proteins. Here, we have investigated the expression of human SERT and DAT on developing megakaryocytes and platelet-like particles derived from the megakaryocyte progenitor cell line MEG-01 upon differentiation by valproic acid (VPA) and all-trans retinoic acid (ATRA). Our results show that MEG-01 cells express SERT and DAT and that VPA and ATRA induce a significant increase of transporter expression on developing megakaryocytes and platelets. As compared to ATRA, VPA more efficiently induced SERT expression but not DAT expression. Comparable to naïve platelets and neurons, SERT was localized to both the cell surface and intracellular compartments. Hence, VPA and ATRA-treated MEG-01 cells provide a model well-suited to studying neuronal monoamine transporter expression, not only during transcription and translation but also with respect to protein trafficking to and from the cell surface.
authors: Department of Child and Adolescent Psychiatry and Psychotherapy, University of Heidelberg/Medical Faculty Mannheim, Mannheim, Germany.
authors: Sarah
authors: S
authors: Hohmann
authors: Nina
authors: N
authors: Schweinfurth
authors: Thorsten
authors: T
authors: Lau
authors: Michael
authors: M
authors: Deuschle
authors: Florian
authors: F
authors: Lederbogen
authors: Tobias
authors: T
authors: Banaschewski
authors: Patrick
authors: P
authors: Schloss
mesh_terms: D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D059290:Dopaminergic Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D055016:Megakaryocyte Progenitor Cells / Q000166:cytology*; D008533:Megakaryocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology; D014404:Tubulin / Q000378:metabolism; D014635:Valproic Acid / Q000494:pharmacology
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; C493214:SLC6A3 protein, human; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D014404:Tubulin; D014212:Tretinoin; D014635:Valproic Acid