Disease relevance of HTR1E

• Furthermore, by means of in situ hybridization to human metaphase chromosomes, using the cloned 5-HT1E receptor gene (phage clone lambda-S31; Levy et al., FEBS Lett. 296:201-206,1992) as was a probe, we demonstrate that this gene is localized to the q14-q15 region on chromosome 6 [1].
• 5-HT1E and 5-HT3 sites were found in neuroblastomas with receptor density and affinity similar to human or rat brain [2].
• In addition, only three glioma cell lines expressed the 5-HT1E receptor [3].

High impact information on HTR1E

• Here, we demonstrate by both MS and biochemical methods that this serine is phosphorylated (S31P) during mitosis in mammalian cells [4].
• Additionally, H3.3 S31P forms a speckled staining pattern on the metaphase plate, whereas H3 S10 and H3 S28 phosphorylation localizes to the outer regions of condensed DNA [4].
• Histone H3.3 contains a serine (S) to alanine (A) replacement at amino acid position 31 (S31) [4].
• Furthermore, in contrast to phosphorylated general H3, H3.3 S31P is localized in distinct chromosomal regions immediately adjacent to centromeres [4].
• In contrast to H3 S10 and H3 S28, which first become phosphorylated in prophase, H3.3 S31 phosphorylation is observed only in late prometaphase and metaphase and is absent in anaphase [4].

Biological context of HTR1E

• The chromosome 6 breakpoint region is gene poor, the closest transcript being the serotonin receptor 1E (HTR1E) at 625 kb telomeric to the breakpoint [5].
• The excellent correlation observed between the pharmacology of the expressed receptor encoded by AC1 and the human brain 5HT1E binding site confirms that AC1 encodes a 5HT1E receptor and establishes a fifth 5HT1-like receptor subtype [6].
• The deduced amino acid sequence of the genomic clone hp75d is identical to that of the recently isolated, but uncharacterized, novel serotonin receptor gene S31 [7].
• We report the molecular cloning of human gene (S31) containing an open reading frame of 1095 nucleotides, which encodes a protein of 365 amino acids [8].
• In this work, we demonstrate by two independent polymerase chain reactions on a panel of human-hamster somatic cell hybrid genomic DNA that the 5-HT1E serotonin receptor gene is localized on human chromosome 6 [1].

Anatomical context of HTR1E

• When expressed transiently in Cos-7 cells, the 5HT1E beta receptor displayed a high affinity for the nonspecific serotonergic radioligand 2-[125I]iodolysergic acid diethylamide (Kd = 980 pM) [9].
• 5-HT1D and 5-HT1E/1F binding sites in depressed suicides: increased 5-HT1D binding in globus pallidus but not cortex [10].
• The present results indicate that sheep caudate nucleus is a valid tissue for studying interaction of compounds with 5-HT1D binding sites in the relative absence of 5-HT1E binding sites [11].
• The highest densities and the highest proportions of 5-HT1E sites were in caudate (72%) and putamen (64%) and the lowest density and lowest proportion in hippocampus (16%) [12].
• In human cortex and hippocampus area, [3H]5-HT (5 nM) labels 5-HT1A, 5-HT1D and 5-HT1E sites [13].

Associations of HTR1E with chemical compounds

• Molecular cloning of a serotonin receptor from human brain (5HT1E): a fifth 5HT1-like subtype [6].
• However, 5-carboxamidotryptamine demonstrated low affinity (pKi = 5.15) compared with serotonin (pKi = 8.14), consistent with the observed binding of the putative 5HT1E receptor [6].
• Fluorescence titration experiments indicated that S31 bound the substrate H2folate 10-fold tighter and the coenzyme NADPH 2-fold tighter than the wild-type human dihydrofolate reductase [14].
• Using oligonucleotide-directed mutagenesis and a bacterial expression system producing the wild-type and mutant human dihydrofolate reductases at levels of 10% of the bacterial protein, we have constructed, expressed, and purified a serine 31 (S31) mutant and a serine 34 (S34) mutant [14].
• The serine 34 mutant had much greater alterations in its properties than S31; specifically, S34 had a 3-fold reduction in the Km for NADPH, a 24-fold increase in the Km for H2folate, a 3-fold reduction in the overall reaction rate kcat, and an 80,000-fold increase in the Kd for methotrexate [14].

Other interactions of HTR1E

• 5-HT1A, 5-HT1D, and 5-HT1E mRNAs were detected in only some patients [15].
• Specific binding at 5-HT1E/F and high-affinity 5-HT2A sites was too low for characterization [16].
• MR77 thus represents a 5-HT receptor of the 5-HT1 class, and we propose that, based on the pharmacological characterization, MR77 represents an additional 5-HT1E-like receptor [17].
• Competition studies with nonradioactive drugs indicated that, of the drugs tested, 5-CT and ergotamine displayed the highest selectivity for the 5-HT1D site versus the 5-HT1E site.(ABSTRACT TRUNCATED AT 250 WORDS)[18]
• No 5-HT1E were detected in choroid plexus, where [3H]5-HT was dramatically reduced by mesulergine (5-HT2C receptors) [13].

Analytical, diagnostic and therapeutic context of HTR1E

• Quantitative autoradiography of 5-HT1D and 5-HT1E binding sites labelled by [3H]5-HT, in frontal cortex and the hippocampal region of the human brain [13].

References