Serotonin-binding proteins

As with the other monoamines, 5-HT is found primarily in storage vesicles (30-35 nm diameter) where serotonin-binding proteins (SBPs) have also been identified. These seem to form a macromolecular complex with 5-HT. In fact, three such proteins have now been characterised, but only one of them, 45kDa SBP, appears to be secreted into the synapse along with 5-HT. Whether they serve any role other than forming an osmotically inert storage matrix for 5-HT is unknown. 

Until recently it was believed that intraneuronal proteins known as serotonin binding proteins (SBP) were involved in the storage, protection, and/or transport of 5-HT (Tamir et al. 1976 Gershon and Tamir 1984) and catecholamines (Jimenez Del Rio et al. 1992,... 

Jimenez Del Rio, M.J. Pinxteren, J. De Potter, W.P. Ebinger, G. and Vauquelin, G. Serotonin-binding proteins in the bovine cerebral cortex Interactions with serotonin and catecholamines. Eur J Pharmacol 225 225-234, 1992. 

Tamir, H. Klein, A. and Rapport, M.M. Serotonin binding protein Enhancement of binding by Fe and inhibition of binding by drugs. JAewrac/zem 26 871-878, 1976. 

Its mechanism of action is not well understood. Some possible actions include inhibition of norepinephrine release and increased re-uptake of norepinephrine and serotonin. It also possibly increases the synthesis and turnover of serotonin. Lithium interferes with the production and release of the second messengers phosphatdylinositol-4,5-bisphosphate and diacyl glycerol. Finally it may uncouple receptor recognition sites from GTP-binding protein by competing with Mg++. 

Mansour, J.M. and Mansour T.E. (1986) GTP-binding proteins associated with serotonin activated adenylate cyclase in Fasciola hepatica. Molecular and Biochemical Parasitology 21, 139-149. 

Leonhardt S, Herrick-Davis K, Teteler M. Detection of a novel serotonin receptor subtype (5-HT1E) in human brain interaction with a GTP-binding protein. 

List of Abbreviations Ach, acetylcholine AMPA, a-amino-3-hydroxy-5-methylisoxazole-4-propionic acid CNS, central nervous system COMT, catechol-O-methyltransferase DA, dopamine DRP-2, dihy-dropyrimidinase-related protein 2 DSM, diagnostic and statistical manual of mental disorders GNAS1, guanine nucleotide-binding protein (G-protein) alpha stimulating activity polypeptide 1 5-HIAA, 5-hydroxyindole acetic acid 5-FIT, serotonin (5-hydroxytryptamine) MAO, monoamine oxidase MHPG, 3-methoxy-4-hydroxyphenylglycol NE, norepinephrine NMDA, N-methyl-D-aspartate PCP, phencyclidine SSRI, selective serotonin reuptake inhibitor SDS, schedule for the deficit syndrome... 

White KJ, Kiser PD, Nichols DE, Barker EL (2006) Engineered zinc-binding sites confirm proximity and orientation of transmembrane helices I and III in the human serotonin transporter. Protein Sci 15 2411-2422... 

Serotonin binds to the platelet 5-HTj receptor coupled to PLC via a G protein. The human serotonin receptor has been cloned and have the usual seven transmembrane domain form (Saltzman et al., 1991). Serotonin is rapidly taken up by passive diffusion and by a high affinity eneigy-dependent carrier, and is released upon platelet activation by secretion ftom the dense granules (Pletscher, 1987). 

The adrenoceptors, both alpha and beta, are members of a receptor superfamily of membrane-spanning proteins, including muscarine, serotonin, and dopamine receptors, that are coupled to intracellular GTP-binding proteins (G-proteins), which determine the cellular response to receptor activation (48). All G-protein-coupled receptors exhibit a common motif of a single polypeptide chain... 

Serotonin, also known as 5-hydroxytryptamine (5-HT) is biosynthesized from tryptophan and is a neurotransmitter. Serotonin plays an important role in many behaviors including sleep, appetite, memory, and mood [52]. People with depressive disorders exhibit low levels of serotonin in the synapses. Protonated serotonin binds to a serotonin reuptake transporter protein, sometimes referred to as the serotonin transporter (SERT) and is then moved to an inward position on the neuron and subsequently released into the cjdoplasm. Selective serotonin reuptake inhibitors (SSRI) bind with high affinity to the serotonin binding site of the transporter. This leads to antidepressant effects by increasing extracellular serotonin levels which in turn enhances serotonin neurotransmission [53]. The SSRI class of antidepressants has fewer side effects than the monoamine oxidase inhibitors. 

---