OCA7 is a melanosome membrane protein that defines pigmentation by regulating early stages of melanosome biogenesis.
OCA7 is a melanosome membrane protein that defines pigmentation by regulating early stages of melanosome biogenesis.
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DOI：
10.1016/j.jbc.2022.102669
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发表时间：
2022-12
影响因子：
4.8
通讯作者：
Di Pietro, Santiago M.
中科院分区：
文献类型：
--
作者：
Beyers, Wyatt C.;Detry, Anna M.;Di Pietro, Santiago M.
C10 orf 11（眼皮肤白化病7型[OCA 7]）的突变导致OCA，这是一种表现为皮肤，眼睛和头发色素减退的疾病。OCA 7的病理生理学尚不清楚，几乎没有关于OCA 7蛋白及其细胞功能的信息。在这里，我们发现OCA 7定位于黑素体的界膜，黑素体是合成黑色素的专门色素细胞器。我们证明，OCA 7是通过与黑素体蛋白Rab 32和Rab 38的典型效应子结合表面相互作用来招募的。使用新生成的OCA 7-KO MNT 1细胞，我们显示OCA 7通过控制黑素体成熟以黑素细胞自主方式调节整体黑素水平。重要的是，我们发现OCA 7调节前黑素体蛋白（PMEL）加工，影响原纤维化和定义从黑素体阶段I到阶段II过渡的条纹。此外，OCA 7-KO细胞的黑素小体腔显示出比对照细胞更低的pH。总之，我们的研究结果表明，OCA 7调节色素沉着，通过两个公认的决定因素黑素体的生物发生和功能，PMEL加工，和细胞器pH值。
Mutations in C10orf11 (oculocutaneous albinism type 7 [OCA7]) cause OCA, a disorder that presents with hypopigmentation in skin, eyes, and hair. The OCA7 pathophysiology is unknown, and there is virtually no information on the OCA7 protein and its cellular function. Here, we discover that OCA7 localizes to the limiting membrane of melanosomes, the specialized pigment cell organelles where melanin is synthesized. We demonstrate that OCA7 is recruited through interaction with a canonical effector–binding surface of melanosome proteins Rab32 and Rab38. Using newly generated OCA7-KO MNT1 cells, we show OCA7 regulates overall melanin levels in a melanocyte autonomous manner by controlling melanosome maturation. Importantly, we found that OCA7 regulates premelanosome protein (PMEL) processing, impacting fibrillation and the striations that define transition from melanosome stage I to stage II. Furthermore, the melanosome lumen of OCA7-KO cells displays lower pH than control cells. Together, our results reveal that OCA7 regulates pigmentation through two well-established determinants of melanosome biogenesis and function, PMEL processing, and organelle pH.
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DOI：
10.1083/jcb.201605090
发表时间：
2016-08-01
期刊：
The Journal of cell biology
影响因子：
--
作者：
Dennis MK;Delevoye C;Acosta-Ruiz A;Hurbain I;Romao M;Hesketh GG;Goff PS;Sviderskaya EV;Bennett DC;Luzio JP;Galli T;Owen DJ;Raposo G;Marks MS
通讯作者：
Marks MS
影响因子：
4.5
作者：
Hellström AR;Watt B;Fard SS;Tenza D;Mannström P;Narfström K;Ekesten B;Ito S;Wakamatsu K;Larsson J;Ulfendahl M;Kullander K;Raposo G;Kerje S;Hallböök F;Marks MS;Andersson L
通讯作者：
Andersson L
影响因子：
20.3
作者：
Ambrosio, Andrea L.;Febvre, Hallie P.;Di Pietro, Santiago M.
通讯作者：
Di Pietro, Santiago M.
影响因子：
3.7
作者：
通讯作者：
--
影响因子：
9.2
作者：
Gerondopoulos, Andreas;Langemeyer, Lars;Liang, Jin-Rui;Linford, Andrea;Barr, Francis A.
通讯作者：
Barr, Francis A.