Department of Dermatology, First Medical Center of PLA General Hospital, Beijing, China.
Department of Dermatology, Chuiyangliu Hospital, Beijing, China.
Exp Dermatol. 2022 Aug;31(8):1253-1263. doi: 10.1111/exd.14586. Epub 2022 May 16.
Recent investigations have shown that the Rab family of GTPases is associated with all aspects of melanogenesis. However, the effect of Rab23, which localizes to the plasma membrane and regulates the endocytic pathway within eukaryotic cells, in melanogenesis has not been reported. To understand the role of Rab23 in UVB-induced melanogenesis, we evaluated changes in the level of melanin, activity of tyrosinase and levels of melanogenesis-related proteins such as microphthalmia transcription factor and tyrosinase-related protein-1 (TRP-1) and the melanosome transport-related protein complex Rab27a-melanophilin-myosin Va after the downregulation of Rab23 in B16F10 and SK-MEL-2 cells with or without UVB irradiation. Our results showed that downregulating Rab23 reduced the melanin level and tyrosinase activity and inhibited the expression of proteins involved in UVB-induced melanogenesis. Rab23 colocalized with mature melanosomes marked with TRP-1. Furthermore, downregulating Rab23 induced the abnormal accumulation of melanosomes around the nucleus. We demonstrated that the downregulation of Rab23 inhibited melanin synthesis and melanosome transport by decreasing the PKA/CREB/MITF pathway, which is the key regulator of UVB-induced melanogenesis.
最近的研究表明，Rab 家族 GTPases 与黑色素生成的各个方面都有关联。然而，Rab23 的作用（定位于质膜并调节真核细胞内的内吞途径）在黑色素生成中的作用尚未被报道。为了了解 Rab23 在 UVB 诱导的黑色素生成中的作用，我们评估了 Rab23 下调后黑色素、酪氨酸酶活性以及黑色素生成相关蛋白（如小眼畸形转录因子和酪氨酸酶相关蛋白-1（TRP-1））和黑素体转运相关蛋白复合物 Rab27a-黑素瘤磷蛋白-myosin Va 的水平变化在 B16F10 和 SK-MEL-2 细胞中有无 UVB 照射。我们的结果表明，下调 Rab23 降低了黑色素水平和酪氨酸酶活性，并抑制了与 UVB 诱导的黑色素生成有关的蛋白表达。Rab23 与用 TRP-1 标记的成熟黑素体共定位。此外，下调 Rab23 诱导黑素体在核周围异常积聚。我们证明，通过降低 PKA/CREB/MITF 通路（UVB 诱导黑色素生成的关键调节剂），下调 Rab23 抑制了黑色素合成和黑素体运输。
