title: Interaction between G Protein-Coupled Receptor 143 and Tyrosinase: Implications for Understanding Ocular Albinism Type 1.
abstract: Developmental eye defects in X-linked ocular albinism type 1 are caused by G-protein coupled receptor 143 (GPR143) mutations. Mutations result in dysfunctional melanosome biogenesis and macromelanosome formation in pigment cells, including melanocytes and retinal pigment epithelium. GPR143, primarily expressed in pigment cells, localizes exclusively to endolysosomal and melanosomal membranes unlike most G protein-coupled receptors, which localize to the plasma membrane. There is some debate regarding GPR143 function and elucidating the role of this receptor may be instrumental for understanding neurogenesis during eye development and for devising therapies for ocular albinism type I. Many G protein-coupled receptors require association with other proteins to function. These G protein-coupled receptor-interacting proteins also facilitate fine-tuning of receptor activity and tissue specificity. We therefore investigated potential GPR143 interaction partners, with a focus on the melanogenic enzyme tyrosinase. GPR143 coimmunoprecipitated with tyrosinase, while confocal microscopy demonstrated colocalization of the proteins. Furthermore, tyrosinase localized to the plasma membrane when coexpressed with a GPR143 trafficking mutant. The physical interaction between the proteins was confirmed using fluorescence resonance energy transfer. This interaction may be required in order for GPR143 to function as a monitor of melanosome maturation. Identifying tyrosinase as a potential GPR143 binding protein opens new avenues for investigating the mechanisms that regulate pigmentation and neurogenesis.
authors.affiliation: Pharmaceutical Chemistry I, PharmaCenter Bonn, University of Bonn, Bonn, Germany.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: De Filippo
authors.affiliation: Pharmaceutical Chemistry I, PharmaCenter Bonn, University of Bonn, Bonn, Germany. Electronic address: schiedel@uni-bonn.de.
authors.forename: Anke C
authors.initials: AC
authors.lastname: Schiedel
authors.affiliation: Ronald O. Perelman, Department of Dermatology, New York University School of Medicine, New York, New York, USA. Electronic address: Prashiela.Manga@nyumc.org.
authors.forename: Prashiela
authors.initials: P
authors.lastname: Manga
mesh_terms: D016117:Albinism, Ocular / Q000209:etiology*; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D005136:Eye Proteins / Q000032:analysis / Q000737:chemistry / Q000502:physiology*; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D008562:Membrane Glycoproteins / Q000032:analysis / Q000737:chemistry / Q000502:physiology*; D014442:Monophenol Monooxygenase / Q000032:analysis / Q000737:chemistry / Q000502:physiology*; D055495:Neurogenesis; D010858:Pigmentation
chemical_list: D005136:Eye Proteins; C095276:GPR143 protein, human; D008562:Membrane Glycoproteins; D014442:Monophenol Monooxygenase