ArticleProceedings of the National Academy of Sciences of the United States of America2011
The ocular albinism type 1 (OA1) GPCR is ubiquitinated and its traffic requires endosomal sorting complex responsible for transport (ESCRT) function.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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21 citing papers in PubMed, 32 citations in OpenAlex.
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- The Many Faces of G Protein-Coupled Receptor 143, an Atypical Intracellular Receptor.Frontiers in molecular biosciences · 2022Review
- Melanosome Biogenesis in the Pigmentation of Mammalian Skin.Integrative and comparative biology · 2021Review
- Post-Translational Modifications of G Protein-Coupled Receptors Control Cellular Signaling Dynamics in Space and Time.Pharmacological reviews · 2021Review
- Polarized human cholangiocytes release distinct populations of apical and basolateral small extracellular vesicles.Molecular biology of the cell · 2020Article
- mTOR complex 1 activity is required to maintain the canonical endocytic recycling pathway against lysosomal delivery.The Journal of biological chemistry · 2017Article
- Odorant Receptor 51E2 Agonist β-ionone Regulates RPE Cell Migration and Proliferation.Frontiers in physiology · 2017Article
- Ocular Albinism Type 1 Regulates Melanogenesis in Mouse Melanocytes.International journal of molecular sciences · 2016Article
- Functional Characterization of the Odorant Receptor 51E2 in Human Melanocytes.The Journal of biological chemistry · 2016Article
- Review
- Gαs regulates the post-endocytic sorting of G protein-coupled receptors.Nature communications · 2014Article
- The complex ultrastructure of the endolysosomal system.Cold Spring Harbor perspectives in biology · 2014Review
- Expression of OA1 limits the fusion of a subset of MVBs with lysosomes - a mechanism potentially involved in the initial biogenesis of melanosomes.Journal of cell science · 2013Article
- PMEL: a pigment cell-specific model for functional amyloid formation.Pigment cell & melanoma research · 2013Review
- Minireview: ubiquitination-regulated G protein-coupled receptor signaling and trafficking.Molecular endocrinology (Baltimore, Md.) · 2013Review
- A dual role for K63-linked ubiquitin chains in multivesicular body biogenesis and cargo sorting.Molecular biology of the cell · 2012Article
- Prostaglandin EP1 receptor down-regulates expression of cyclooxygenase-2 by facilitating its proteasomal degradation.The Journal of biological chemistry · 2012Article
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3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The function of signaling receptors is tightly controlled by their intracellular trafficking. One major regulatory mechanism within the endo-lysosomal system required for receptor localization and down-regulation is protein modification by ubiquitination and downstream interactions with the endosomal sorting complex responsible for transport (ESCRT) machinery. Whether and how these mechanisms operate to regulate endosomal sorting of mammalian G protein-coupled receptors (GPCRs) remains unclear. Here, we explore the involvement of ubiquitin and ESCRTs in the trafficking of OA1, a pigment cell-specific GPCR, target of mutations in Ocular Albinism type 1, which localizes intracellularly to melanosomes to regulate their biogenesis. Using biochemical and morphological methods in combination with overexpression and inactivation approaches we show that OA1 is ubiquitinated and that its intracellular sorting and down-regulation requires functional ESCRT components. Depletion or overexpression of subunits of ESCRT-0, -I, and -III markedly inhibits OA1 degradation with concomitant retention within the modified endosomal system. Our data further show that OA1 ubiquitination is uniquely required for targeting to the intralumenal vesicles of multivesicular endosomes, thereby regulating the balance between down-regulation and delivery to melanosomes. This study highlights the role of ubiquitination and the ESCRT machinery in the intracellular trafficking of mammalian GPCRs and has implications for the physiopathology of ocular albinism type 1.
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