The melanosomal/lysosomal protein OA1 has properties of a G protein-coupled receptor

Giulio Innamorati, Rosanna Piccirillo, Paola Bagnato, Ilaria Palmisano, Maria Vittoria Schiaffino

Research output: Contribution to journalArticle

Abstract

The protein product of the ocular albinism type 1 gene, named OA1, is a pigment cell-specific integral membrane glycoprotein, localized to melanosomes and lysosomes and possibly implicated in melanosome biogenesis. Although its function remains unknown, we previously showed that OA1 shares structural similarities with G protein-coupled receptors (GPCRs). To ascertain the molecular function of OA1 and in particular its nature as a GPCR, we adopted a heterologous expression strategy commonly exploited to demonstrate GPCR-mediated signaling in mammalian cells. Here we show that when expressed in COS7 cells OA1 displays a considerable and spontaneous capacity to activate heterotrimeric G proteins and the associated signaling cascade. In contrast, OA1 mutants carrying either a missense mutation or a small deletion in the third cytosolic loop lack this ability. Furthermore, OA1 is phosphorylated and interacts with arrestins, well-established multifunctional adaptors of conformationally active GPCRs. In fact, OA1 colocalizes and coprecipitates with arrestins, which downregulate the signaling of OA1 by specifically reducing its expression levels. These findings indicate that heterologously expressed OA1 exhibits two fundamental properties of GPCRs, being capable to activate heterotrimeric G proteins and to functionally associate with arrestins, and provide proof of principle that OA1 can actually function as a canonical GPCR in mammalian cells.

Original languageEnglish
Pages (from-to)125-135
Number of pages11
JournalPigment Cell Research
Volume19
Issue number2
DOIs
Publication statusPublished - Apr 2006

Fingerprint

G-Protein-Coupled Receptors
Arrestins
arrestins
Melanosomes
Heterotrimeric GTP-Binding Proteins
proteins
G-proteins
Cells
cells
membrane glycoproteins
missense mutation
protein products
Membrane Glycoproteins
lysosomes
Missense Mutation
Lysosomes
albino
Pigments
lysosomal proteins
G-protein coupled receptors

Keywords

  • Arrestin
  • G protein
  • G protein-coupled receptors
  • Lysosome
  • Melanosome
  • Ocular albinism

ASJC Scopus subject areas

  • Agronomy and Crop Science
  • Plant Science
  • Cell Biology
  • Clinical Biochemistry
  • Developmental Biology

Cite this

The melanosomal/lysosomal protein OA1 has properties of a G protein-coupled receptor. / Innamorati, Giulio; Piccirillo, Rosanna; Bagnato, Paola; Palmisano, Ilaria; Schiaffino, Maria Vittoria.

In: Pigment Cell Research, Vol. 19, No. 2, 04.2006, p. 125-135.

Research output: Contribution to journalArticle

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