Institut Curie, PSL Research University, CNRS, UMR144, Structure and Membrane Compartments, F-75005 Paris, France.
Institut Curie, PSL Research University, CNRS, UMR144, Cell and Tissue Imaging Facility (PICT-IBiSA), F-75005 Paris, France.
Int J Mol Sci. 2018 Feb 14;19(2):568. doi: 10.3390/ijms19020568.
Melanocytes are specialized cells that generate unique organelles called melanosomes in which melanin is synthesized and stored. Melanosome biogenesis and melanocyte pigmentation require the transport and delivery of melanin synthesizing enzymes, such as tyrosinase and related proteins (e.g., TYRP1), from endosomes to maturing melanosomes. Among the proteins controlling endosome-melanosome transport, AP-1 together with KIF13A coordinates the endosomal sorting and trafficking of TYRP1 to melanosomes. We identify here β1-adaptin AP-1 subunit-derived peptides of 5 amino acids that block the interaction of KIF13A with AP-1 in cells. Incubating these peptides with human MNT-1 cells or 3D-reconstructed pigmented epidermis decreases pigmentation by impacting the maturation of melanosomes in fully pigmented organelles. This study highlights that peptides targeting the intracellular trafficking of melanocytes are candidate molecules to tune pigmentation in health and disease.
黑素细胞是专门的细胞，它们在其中生成称为黑素小体的独特细胞器，黑色素在其中合成和储存。黑素小体的生物发生和黑素细胞的色素沉着需要黑色素合成酶（如酪氨酸酶和相关蛋白（例如，TYRP1））从内体运输和递送到成熟的黑素小体。在控制内体-黑素小体运输的蛋白质中，AP-1 与 KIF13A 一起协调 TYRP1 到黑素小体的内体分拣和运输。我们在这里鉴定了源自 5 个氨基酸的 β1-衔接蛋白 AP-1 亚基衍生肽，这些肽在细胞中阻断 KIF13A 与 AP-1 的相互作用。用这些肽孵育人 MNT-1 细胞或 3D 重建的色素化表皮会通过影响完全色素化细胞器中黑素小体的成熟来减少色素沉着。这项研究强调，针对黑素细胞细胞内运输的肽是调节健康和疾病中色素沉着的候选分子。
