2026-10-11T14:45:59Z https://api.figshare.com/v2/oai

oai:figshare.com:article/33763901 2026-09-14T22:04:46Z category_4 category_12 category_14 category_15 category_61 category_64 category_122 category_132 portal_63 item_type_3 month_year_09_2026

Proximity Labeling of D1-Like Dopamine Receptors Captures Distinct Cellular Environments and Uncovers Trafficking Proteins That Regulate DA-Mediated Behaviors in Drosophila Dana C. Guhle (24905801) Bhavana Kanagala (24905804) Rebecca Dust (24905807) Ross Evashkevich (24905810) Ronald L. Davis (9294815) Jacob A. Berry (9294818) Biochemistry Cell Biology Molecular Biology Neuroscience Developmental Biology Cancer Mental Health Infectious Diseases uncovers trafficking proteins mediated endocytosis pathways mediated camp responses arrestin 2 ), turbo showed ligand specific subcellular environments like da receptors mediated proximity labeling drosophila </ italic arrestin 2 proximity labeling mediated behaviors drosophila </ specific signaling driven proximity mediated learning vivo </ proximal environments cellular environments activation environments wash complex synaptic regulation synaptic functions show evidence remain uncharacterized regulate r1 recruit β neurotransmitter dopamine multifunctional role memory circuits induced attraction human cells distinct domains comparative characterization cell surface The neurotransmitter dopamine (DA) is central to synaptic regulation that supports diverse behavioral functions, including both learning and forgetting. This multifunctional role of DA is due to receptor-specific signaling in specific subcellular environments that remain uncharacterized. Here we used Turbo-mediated proximity labeling in human cells to characterize the proximal environments of two <i>Drosophila</i> D1-like DA receptors (Dop1R1 and Dop1R2) in basal and DA-activation environments. DA drives both Dop1R1-Turbo and Dop1R2-Turbo to recruit β-arrestin 2, and Dop1R1-Turbo showed ligand-driven proximity to G-protein receptor kinase 3, members of clathrin-mediated endocytosis pathways, and WASH complex-mediated endosomal trafficking pathways. Additionally, we show evidence that Dop1R1 and Dop1R2 reside in distinct domains on the cell surface. <i>In vivo</i> disruption of <i>Drosophila</i> orthologues of Dop1R proximal proteins revealed three trafficking proteins, Sec24AB, Krz (beta-arrestin 2), and CG13887, that regulate R1-mediated learning, starvation-induced attraction to odors, and DA-mediated cAMP responses in memory circuits. In addition to revealing DA receptor trafficking proteins that support learning, our comparative characterization of the cellular environments of D1-like receptors offers insights into how DA differentially regulates diverse behavioral and synaptic functions. 2026-09-14T00:00:00Z Dataset Dataset 10.1021/acs.jproteome.6c00259.s002 https://figshare.com/articles/dataset/Proximity_Labeling_of_D1-Like_Dopamine_Receptors_Captures_Distinct_Cellular_Environments_and_Uncovers_Trafficking_Proteins_That_Regulate_DA-Mediated_Behaviors_in_Drosophila/33763901 CC BY-NC 4.0