Sharma, Ashwani; Kumar, G. Aditya; Chattopadhyay, Amitabha published the artcile< Late endosomal/lysosomal accumulation of a neurotransmitter receptor in a cellular model of Smith-Lemli-Opitz syndrome>, Electric Literature of 434-16-2, the main research area is Smith Lemli Opitz syndrome neurotransmitter receptor; 7-DHC; AY 9944; SLOS; altered trafficking; cholesterol; serotonin1A receptor.
Smith-Lemli-Opitz syndrome (SLOS) is a congenital and developmental malformation syndrome associated with defective cholesterol biosynthesis. It is characterized by accumulation of 7-dehydrocholesterol (the immediate biosynthetic precursor of cholesterol in the Kandutsch-Russell pathway) and an altered cholesterol to total sterol ratio. Because SLOS is associated with neurol. malfunction, exploring the function and trafficking of neuronal receptors and their interaction with membrane lipids under these conditions assume significance. In this work, we generated a cellular model of SLOS in HEK-293 cells stably expressing the human serotonin1A receptor (an important neurotransmitter G-protein coupled receptor) using AY 9944, an inhibitor for the enzyme 3β-hydroxy-steroid-Δ7-reductase (7-DHCR). Using a quant. flow cytometry based assay, we show that the plasma membrane population of serotonin1A receptors was considerably reduced under these conditions without any change in total cellular expression of the receptor. Interestingly, the receptors were trafficked to sterol-enriched LysoTracker pos. compartments, which accumulated under these conditions. To the best of our knowledge, our results constitute one of the first reports demonstrating intracellular accumulation and misregulated traffic of a neurotransmitter GPCR in SLOS-like conditions. We believe these results assume relevance in our overall understanding of the mol. basis underlying the functional relevance of neurotransmitter receptors in SLOS.
Traffic (Oxford, United Kingdom) published new progress about 5-HT1A receptors Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 434-16-2 belongs to class alcohols-buliding-blocks, and the molecular formula is C27H44O, Electric Literature of 434-16-2.
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