TY - JOUR
T1 - Melanosome-autonomous regulation of size and number
T2 - The OA1 receptor sustains PMEL expression
AU - Falletta, Paola
AU - Bagnato, Paola
AU - Bono, Maria
AU - Monticone, Massimiliano
AU - Schiaffino, Maria Vittoria
AU - Bennett, Dorothy C.
AU - Goding, Colin R.
AU - Tacchetti, C.
AU - Valetti, C.
PY - 2014
Y1 - 2014
N2 - Summary: 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.
AB - Summary: 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.
KW - Melanosome biogenesis
KW - Microphthalmia-associated transcription factor
KW - Ocular Albinism type 1
UR - http://www.scopus.com/inward/record.url?scp=84902551248&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84902551248&partnerID=8YFLogxK
U2 - 10.1111/pcmr.12239
DO - 10.1111/pcmr.12239
M3 - Article
C2 - 24650003
AN - SCOPUS:84902551248
VL - 27
SP - 565
EP - 579
JO - Pigment Cell and Melanoma Research
JF - Pigment Cell and Melanoma Research
SN - 1755-1471
IS - 4
ER -