日本香粧品学会誌

Vol. 43, No. 1, pp. 28–31（2019）〈教育セミナー〉
第 43 回教育セミナー（2018）・「健やかな肌を保つ―エイジングケア最前線―」

メラニン合成酵素およびメラノソーム輸送の分子機構—輸送阻害に着目した美白剤開発—

福 田 光 則*Molecular Mechanisms of Melanogenic Enzyme Transport and Melanosome Transport:
Development of New Cosmetics That Inhibit Transport Machineries
Mitsunori FUKUDA*
Abstract
Melanin pigments play a pivotal role in protecting our body from harmful ultraviolet radiation, but their excess deposition often causes freckles and skin spots. To prevent undesirable melanin deposition, it is important to understand the molecular mechanisms of formation, maturation, and transport of melanosomes, specialized organelles that synthesize and store
melanin in melanocytes. Melanosomes are formed and matured at the perinuclear region of melanocytes (step 1). In this step,melanogenic enzymes such as tyrosinase and tyrosinase-related protein 1 (Tyrp1) are transported to immature melanosomes
by several protein complexes such as BLOC-1–3 complexes and a complex composed of small GTPases Rab32/38, their effector Varp, and v-SNARE VAMP7. Mature melanosomes are ﬁrst transported from the perinucleus to the cell periphery by
microtubule-dependent motors such as Kif5b (i.e., Rab1A/SKIP/Kif5b complex) (step 2) and then transported to just beneaththe plasma membrane by an actin-dependent motor myosin-Va (i.e., Rab27A/Slac2-a/myosin-Va complex) (step 3). The melanosomes anchored to the plasma membrane are ﬁnally transferred to neighboring keratinocytes or hair matrix cells throughdendrites of melanocytes (step 4) to achieve skin and hair pigmentation. Recent advances in molecular biology techniques
have allowed us to dissect the molecular machineries regulating each melanosome transport step. For example, knockdown
of Varp by speciﬁc siRNAs or overexpression of Varp in melanocytes inhibits transport of melanogenic enzymes to immaturemelanosomes, which leads to a hypopigmentation phenotype in cultured melanocytes. On the other hand, functional ablationof Rab27A or its effector Slac2-a inhibits actin-based melanosome transport, which leads to a perinuclear melanosome aggregation phenotype (i.e., typical phenotype observed in melanocytes from Griscelli syndrome patients). Thus, screening andidentiﬁcation of new substances or plant extracts that inhibit (or promote) the function of these transport machineries will enable us to develop new cosmetics for skin whitening (or new drugs that prevent gray hair) in the future.
Key words: melanosome transport, melanogenic enzymes, Rab small GTPases, melanocyte, keratinocyte.

1.

細胞骨格と呼ばれる 2 種類の道路に沿って，まず細胞のはじめに辺縁部へと輸送されます（ステップ❷❸）。その後，メラ肌や髪の毛に含まれるメラニン色素は，有害な紫外ノソームはメラノサイトの樹状突起から隣接する肌や毛線から私たちの体を守るという生物学的に重要な役割を髪を作る細胞（ケラチノサイトや毛母細胞）へと受け渡担う一方で，加齢などによるメラニン色素の過剰な沈着され（ステップ❹），初めて肌や髪の暗色化が起こりますはシミの原因ともなります。メラニン色素の沈着を人為（Fig. 1 中段）。このようにメラノソーム内で合成された的に防ぐためには，まずその仕組みを知ることが大切でメラニン色素が実際に働くまでには，非常に複雑な長いす。メラニン色素は，メラノサイトと呼ばれる特殊な細道のり（すなわち『輸送』のプロセス）が必要なわけです。

胞に存在する小胞状の細胞小器官，「メラノソーム」の中

近年の分子細胞生物学の目覚ましい発展により，これらで合成・貯蔵されています（ステップ❶）。核の周辺で形の輸送の分子機構の一端が明らかになり 1, 2），新たな視点

成・成熟したメラノソームは，細胞内に張り巡らされたでの美白剤開発が可能となってきています 3）。本稿では，

東北大学大学院

生命科学研究科* Corresponding author：東北大学大学院 生命科学研究科，〒980–8578 仙台市青葉区荒巻字青葉 6–3（E-mail: nori@m.tohoku.ac.jp）

Graduate School of Life Sciences, Tohoku University (6–3 Aoba,Aramaki, Aoba-ku, Sendai 980–8578, Japan)