Melanosome‐autonomous regulation of size and number: the OA 1 receptor sustains PMEL expression

• Published in: Pigment cell and melanoma research 2014-07, Vol.27 (4), p.565-579
• Main Authors: Falletta, Paola, Bagnato, Paola, Bono, Maria, Monticone, Massimiliano, Schiaffino, Maria Vittoria, Bennett, Dorothy C., Goding, Colin R., Tacchetti, Carlo, Valetti, Caterina
• Format: Article
• Language: English
• ISSN: 1755-1471; 1755-148X
• DOI: 10.1111/pcmr.12239

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. OA 1 is a melanosome‐associated G ‐protein‐coupled receptor involved in melanosome biogenesis during melanocyte differentiation. Cells lacking OA 1 contain fewer, but larger, mature melanosomes. Here, we show that OA 1 loss of function reduces both the basal expression and the α‐melanocyte‐stimulating hormone/c AMP ‐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, OA 1 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.