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Melanosome-autonomous regulation of size and number: the OA1 receptor sustains PMEL expression.

Falletta, P; Bagnato, P; Bono, M; Monticone, M; Schiaffino, MV; Bennett, DC; Goding, CR; Tacchetti, C; Valetti, C (2014) Melanosome-autonomous regulation of size and number: the OA1 receptor sustains PMEL expression. Pigment Cell Melanoma Res, 27 (4). pp. 565-579. ISSN 1755-148X https://doi.org/10.1111/pcmr.12239
SGUL Authors: Bennett, Dorothy Catherine

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Abstract

Little is known as to how cells ensure that organelle size and number are coordinated to correctly couple organelle biogenesis to the demands of proliferation or differentiation. OA1 is a melanosome-associated G-protein-coupled receptor involved in melanosome biogenesis during melanocyte differentiation. Cells lacking OA1 contain fewer, but larger, mature melanosomes. Here, we show that OA1 loss of function reduces both the basal expression and the α-melanocyte-stimulating hormone/cAMP-dependent induction of the microphthalmia-associated transcription factor (MITF), the master regulator of melanocyte differentiation. In turn, this leads to a significant reduction in expression of PMEL, a major melanosomal structural protein, but does not affect tyrosinase and melanin levels. In line with its pivotal role in sensing melanosome maturation, OA1 expression rescues melanosome biogenesis, activates MITF expression and thereby coordinates melanosome size and number, providing a quality control mechanism for the organelle in which resides. Thus, resident sensor receptors can activate a transcriptional cascade to specifically promote organelle biogenesis.

Item Type: Article
Additional Information: This is the peer reviewed version of the following article: Falletta, P., Bagnato, P., Bono, M., Monticone, M., Schiaffino, M. V., Bennett, D. C., Goding, C. R., Tacchetti, C. and Valetti, C. (2014), Melanosome-autonomous regulation of size and number: the OA1 receptor sustains PMEL expression. Pigment Cell Melanoma Res., 27: 565–579., which has been published in final form at http://doi.org/10.1111/pcmr.12239. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
Keywords: Ocular Albinism type 1, melanosome biogenesis, microphthalmia-associated transcription factor, Animals, Base Sequence, Cell Differentiation, Cell Line, Eye Proteins, Gene Expression Regulation, Humans, Melanocytes, Melanosomes, Membrane Glycoproteins, Mice, Mice, Knockout, Microphthalmia-Associated Transcription Factor, Molecular Sequence Data, Receptors, G-Protein-Coupled, alpha-MSH, gp100 Melanoma Antigen, Cell Line, Melanosomes, Melanocytes, Animals, Mice, Knockout, Humans, Mice, alpha-MSH, Eye Proteins, Membrane Glycoproteins, Receptors, G-Protein-Coupled, Cell Differentiation, Gene Expression Regulation, Base Sequence, Molecular Sequence Data, Microphthalmia-Associated Transcription Factor, gp100 Melanoma Antigen, melanosome biogenesis, Ocular Albinism type 1, microphthalmia-associated transcription factor, melanosome biogenesis, Ocular Albinism type 1, microphthalmia-associated transcription factor, OCULAR ALBINISM TYPE-1, PROTEIN-COUPLED RECEPTOR, MICROPHTHALMIA GENE-PRODUCT, SILVER LOCUS, RETROVIRAL VECTORS, HUMAN MELANOCYTES, TRANSCRIPTION, BIOGENESIS, TYROSINASE, MITF, 06 Biological Sciences, 11 Medical And Health Sciences
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) > Cell Sciences (INCCCS)
Journal or Publication Title: Pigment Cell Melanoma Res
ISSN: 1755-148X
Language: eng
Dates:
DateEvent
July 2014Published
20 March 2014Published Online
17 March 2014Accepted
Publisher License: Publisher's own licence
Projects:
Project IDFunderFunder ID
GGP02443TelethonUNSPECIFIED
GGP08156TelethonUNSPECIFIED
PubMed ID: 24650003
Web of Science ID: WOS:000337619700010
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/108944
Publisher's version: https://doi.org/10.1111/pcmr.12239

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