The ocular albinism type 1 protein, an intracellular G protein-coupled receptor, regulates melanosome transport in pigment cells

Ilaria Palmisano, Paola Bagnato, Angela Palmigiano, Giulio Innamorati, Giuseppe Rotondo, Domenico Altimare, Consuelo Venturi, Elena V. Sviderskaya, Rosanna Piccirillo, Massimiliano Coppola, Valeria Marigo, Barbara Incerti, Andrea Ballabio, Enrico M. Surace, Carlo Tacchetti, Dorothy C. Bennett, Maria Vittoria Schiaffino

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

The protein product of the ocular albinism type 1 gene, named OA1, is a pigment cell-specific G protein-coupled receptor exclusively localized to intracellular organelles, namely lysosomes and melanosomes. Loss of OA1 function leads to the formation of macromelanosomes, suggesting that this receptor is implicated in organelle biogenesis, however the mechanism involved in the pathogenesis of the disease remains obscure. We report here the identification of an unexpected abnormality in melanosome distribution both in retinal pigment epithelium (RPE) and skin melanocytes of Oa1-knock-out (KO) mice, consisting in a displacement of the organelles from the central cytoplasm towards the cell periphery. Despite their depletion from the microtubule (MT)-enriched perinuclear region, Oa1-KO melanosomes were able to aggregate at the centrosome upon disruption of the actin cytoskeleton or expression of a dominant-negative construct of myosin Va. Consistently, quantification of organelle transport in living cells revealed that Oa1-KO melanosomes displayed a severe reduction in MT-based motility; however, this defect was rescued to normal following inhibition of actin-dependent capture at the cell periphery. Together, these data point to a defective regulation of organelle transport in the absence of OA1 and imply that the cytoskeleton might represent a downstream effector of this receptor. Furthermore, our results enlighten a novel function for OA1 in pigment cells and suggest that ocular albinism type 1 might result from a different pathogenetic mechanism than previously thought, based on an organelle-autonomous signalling pathway implicated in the regulation of both membrane traffic and transport.

Original languageEnglish
Pages (from-to)3487-3501
Number of pages15
JournalHuman Molecular Genetics
Volume17
Issue number22
DOIs
Publication statusPublished - 2008

Fingerprint

Melanosomes
G-Protein-Coupled Receptors
Organelles
Proteins
Microtubules
Centrosome
Retinal Pigment Epithelium
Melanocytes
Organelle Biogenesis
Myosins
Lysosomes
Cytoskeleton
Actin Cytoskeleton
Knockout Mice
Actins
Cytoplasm
Ocular Albinism type 1
Skin
Membranes
Genes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Molecular Biology

Cite this

The ocular albinism type 1 protein, an intracellular G protein-coupled receptor, regulates melanosome transport in pigment cells. / Palmisano, Ilaria; Bagnato, Paola; Palmigiano, Angela; Innamorati, Giulio; Rotondo, Giuseppe; Altimare, Domenico; Venturi, Consuelo; Sviderskaya, Elena V.; Piccirillo, Rosanna; Coppola, Massimiliano; Marigo, Valeria; Incerti, Barbara; Ballabio, Andrea; Surace, Enrico M.; Tacchetti, Carlo; Bennett, Dorothy C.; Schiaffino, Maria Vittoria.

In: Human Molecular Genetics, Vol. 17, No. 22, 2008, p. 3487-3501.

Research output: Contribution to journalArticle

Palmisano, I, Bagnato, P, Palmigiano, A, Innamorati, G, Rotondo, G, Altimare, D, Venturi, C, Sviderskaya, EV, Piccirillo, R, Coppola, M, Marigo, V, Incerti, B, Ballabio, A, Surace, EM, Tacchetti, C, Bennett, DC & Schiaffino, MV 2008, 'The ocular albinism type 1 protein, an intracellular G protein-coupled receptor, regulates melanosome transport in pigment cells', Human Molecular Genetics, vol. 17, no. 22, pp. 3487-3501. https://doi.org/10.1093/hmg/ddn241
Palmisano, Ilaria ; Bagnato, Paola ; Palmigiano, Angela ; Innamorati, Giulio ; Rotondo, Giuseppe ; Altimare, Domenico ; Venturi, Consuelo ; Sviderskaya, Elena V. ; Piccirillo, Rosanna ; Coppola, Massimiliano ; Marigo, Valeria ; Incerti, Barbara ; Ballabio, Andrea ; Surace, Enrico M. ; Tacchetti, Carlo ; Bennett, Dorothy C. ; Schiaffino, Maria Vittoria. / The ocular albinism type 1 protein, an intracellular G protein-coupled receptor, regulates melanosome transport in pigment cells. In: Human Molecular Genetics. 2008 ; Vol. 17, No. 22. pp. 3487-3501.
@article{575e686cb4044c3ea0c394a67860ede9,
title = "The ocular albinism type 1 protein, an intracellular G protein-coupled receptor, regulates melanosome transport in pigment cells",
abstract = "The protein product of the ocular albinism type 1 gene, named OA1, is a pigment cell-specific G protein-coupled receptor exclusively localized to intracellular organelles, namely lysosomes and melanosomes. Loss of OA1 function leads to the formation of macromelanosomes, suggesting that this receptor is implicated in organelle biogenesis, however the mechanism involved in the pathogenesis of the disease remains obscure. We report here the identification of an unexpected abnormality in melanosome distribution both in retinal pigment epithelium (RPE) and skin melanocytes of Oa1-knock-out (KO) mice, consisting in a displacement of the organelles from the central cytoplasm towards the cell periphery. Despite their depletion from the microtubule (MT)-enriched perinuclear region, Oa1-KO melanosomes were able to aggregate at the centrosome upon disruption of the actin cytoskeleton or expression of a dominant-negative construct of myosin Va. Consistently, quantification of organelle transport in living cells revealed that Oa1-KO melanosomes displayed a severe reduction in MT-based motility; however, this defect was rescued to normal following inhibition of actin-dependent capture at the cell periphery. Together, these data point to a defective regulation of organelle transport in the absence of OA1 and imply that the cytoskeleton might represent a downstream effector of this receptor. Furthermore, our results enlighten a novel function for OA1 in pigment cells and suggest that ocular albinism type 1 might result from a different pathogenetic mechanism than previously thought, based on an organelle-autonomous signalling pathway implicated in the regulation of both membrane traffic and transport.",
author = "Ilaria Palmisano and Paola Bagnato and Angela Palmigiano and Giulio Innamorati and Giuseppe Rotondo and Domenico Altimare and Consuelo Venturi and Sviderskaya, {Elena V.} and Rosanna Piccirillo and Massimiliano Coppola and Valeria Marigo and Barbara Incerti and Andrea Ballabio and Surace, {Enrico M.} and Carlo Tacchetti and Bennett, {Dorothy C.} and Schiaffino, {Maria Vittoria}",
year = "2008",
doi = "10.1093/hmg/ddn241",
language = "English",
volume = "17",
pages = "3487--3501",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "22",

}

TY - JOUR

T1 - The ocular albinism type 1 protein, an intracellular G protein-coupled receptor, regulates melanosome transport in pigment cells

AU - Palmisano, Ilaria

AU - Bagnato, Paola

AU - Palmigiano, Angela

AU - Innamorati, Giulio

AU - Rotondo, Giuseppe

AU - Altimare, Domenico

AU - Venturi, Consuelo

AU - Sviderskaya, Elena V.

AU - Piccirillo, Rosanna

AU - Coppola, Massimiliano

AU - Marigo, Valeria

AU - Incerti, Barbara

AU - Ballabio, Andrea

AU - Surace, Enrico M.

AU - Tacchetti, Carlo

AU - Bennett, Dorothy C.

AU - Schiaffino, Maria Vittoria

PY - 2008

Y1 - 2008

N2 - The protein product of the ocular albinism type 1 gene, named OA1, is a pigment cell-specific G protein-coupled receptor exclusively localized to intracellular organelles, namely lysosomes and melanosomes. Loss of OA1 function leads to the formation of macromelanosomes, suggesting that this receptor is implicated in organelle biogenesis, however the mechanism involved in the pathogenesis of the disease remains obscure. We report here the identification of an unexpected abnormality in melanosome distribution both in retinal pigment epithelium (RPE) and skin melanocytes of Oa1-knock-out (KO) mice, consisting in a displacement of the organelles from the central cytoplasm towards the cell periphery. Despite their depletion from the microtubule (MT)-enriched perinuclear region, Oa1-KO melanosomes were able to aggregate at the centrosome upon disruption of the actin cytoskeleton or expression of a dominant-negative construct of myosin Va. Consistently, quantification of organelle transport in living cells revealed that Oa1-KO melanosomes displayed a severe reduction in MT-based motility; however, this defect was rescued to normal following inhibition of actin-dependent capture at the cell periphery. Together, these data point to a defective regulation of organelle transport in the absence of OA1 and imply that the cytoskeleton might represent a downstream effector of this receptor. Furthermore, our results enlighten a novel function for OA1 in pigment cells and suggest that ocular albinism type 1 might result from a different pathogenetic mechanism than previously thought, based on an organelle-autonomous signalling pathway implicated in the regulation of both membrane traffic and transport.

AB - The protein product of the ocular albinism type 1 gene, named OA1, is a pigment cell-specific G protein-coupled receptor exclusively localized to intracellular organelles, namely lysosomes and melanosomes. Loss of OA1 function leads to the formation of macromelanosomes, suggesting that this receptor is implicated in organelle biogenesis, however the mechanism involved in the pathogenesis of the disease remains obscure. We report here the identification of an unexpected abnormality in melanosome distribution both in retinal pigment epithelium (RPE) and skin melanocytes of Oa1-knock-out (KO) mice, consisting in a displacement of the organelles from the central cytoplasm towards the cell periphery. Despite their depletion from the microtubule (MT)-enriched perinuclear region, Oa1-KO melanosomes were able to aggregate at the centrosome upon disruption of the actin cytoskeleton or expression of a dominant-negative construct of myosin Va. Consistently, quantification of organelle transport in living cells revealed that Oa1-KO melanosomes displayed a severe reduction in MT-based motility; however, this defect was rescued to normal following inhibition of actin-dependent capture at the cell periphery. Together, these data point to a defective regulation of organelle transport in the absence of OA1 and imply that the cytoskeleton might represent a downstream effector of this receptor. Furthermore, our results enlighten a novel function for OA1 in pigment cells and suggest that ocular albinism type 1 might result from a different pathogenetic mechanism than previously thought, based on an organelle-autonomous signalling pathway implicated in the regulation of both membrane traffic and transport.

UR - http://www.scopus.com/inward/record.url?scp=54949125380&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=54949125380&partnerID=8YFLogxK

U2 - 10.1093/hmg/ddn241

DO - 10.1093/hmg/ddn241

M3 - Article

C2 - 18697795

AN - SCOPUS:54949125380

VL - 17

SP - 3487

EP - 3501

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 22

ER -