title: Melanosome-autonomous regulation of size and number: the OA1 receptor sustains PMEL expression.
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.
authors.affiliation: Department of Experimental Medicine, University of Genoa, Genoa, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Falletta
authors.forename: Paola
authors.initials: P
authors.lastname: Bagnato
authors.forename: Maria
authors.initials: M
authors.lastname: Bono
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Monticone
authors.forename: Maria Vittoria
authors.initials: MV
authors.lastname: Schiaffino
authors.forename: Dorothy C
authors.initials: DC
authors.lastname: Bennett
authors.forename: Colin R
authors.initials: CR
authors.lastname: Goding
authors.forename: Carlo
authors.initials: C
authors.lastname: Tacchetti
authors.forename: Caterina
authors.initials: C
authors.lastname: Valetti
mesh_terms: D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D008544:Melanocytes / Q000166:cytology / Q000378:metabolism*; D020460:Melanosomes; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D051739:Microphthalmia-Associated Transcription Factor / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D000521:alpha-MSH / Q000235:genetics / Q000378:metabolism; D058951:gp100 Melanoma Antigen / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D005136:Eye Proteins; C095276:GPR143 protein, human; C506821:Gpr143 protein, mouse; C497234:MITF protein, human; D008562:Membrane Glycoproteins; D051739:Microphthalmia-Associated Transcription Factor; C497235:Mitf protein, mouse; C548637:PMEL protein, human; D043562:Receptors, G-Protein-Coupled; D058951:gp100 Melanoma Antigen; D000521:alpha-MSH
keywords: Ocular Albinism type 1; melanosome biogenesis; microphthalmia-associated transcription factor