Abstract
Myosin Va (Myo Va) is one of three protein complexes involved in melanosome transport. In this study, we identified BMP-2 as an up-regulator of Myo Va expression using 2-methyl-naphtho[1,2,3-de]quinolin-8-one (MNQO). Our results showed that MNQO reduced the mRNA and protein expression of Myo Va and BMP-2 in melanocytes. Knockdown of BMP-2 by siRNA also affected Myo Va mRNA and protein expression, confirming that MNQO regulates Myo Va through BMP-2. Furthermore, phosphorylation of Smad1/5/8 by BMP2 treatment confirmed that the BMP-2/Smad signaling pathway regulates Myo Va expression in Melan-a melanocytes. Smad-binding elements were found in the Myo Va promoter and phosphorylated Smad1/5/8 bind directly to the Myo Va promoter to activate Myo Va transcription and BMP-2 enhances this binding. These findings provide insight into a new role for BMP-2 in Melan-a melanocytes and a mechanism of regulation of Myo Va expression that may be beneficial in the treatment of albinism or hyperpigmentation disorders.
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs00403-024-02955-9/MediaObjects/403_2024_2955_Fig1_HTML.png)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs00403-024-02955-9/MediaObjects/403_2024_2955_Fig2_HTML.png)
Data availability
No datasets were generated or analysed during the current study.
References
Brenner M, Hearing VJ The protective role of melanin against UV damage in human skin. Photochem Photobiol 2008 May-Jun ;84(3):539–549
Urabe K, Nakayama J, Hori Y (1998) Mixed epidermal and dermal hypermelanoses. In: Nordlund JJ, Boissy RE, Hearing VJ, King RA, Oetting WS, Ortonne JP (eds) The Pigmentary System: physiology and pathophysiology. Oxford University Press, New York, NY, USA, pp 909–913
Wasmeier C, Hume AN, Bolasco G, Seabra MC (2008) Melanosomes at a glance. J Cell Sci 121:3995–3999
Van Gele M, Dynoodt P, Lambert J (2009) Griscelli syndrome: a model system to study vesicular trafficking. Pigment Cell Melanoma Res 22:268–282
Tarafder AK, Wasmeier C, Figueiredo AC, Booth AE, Orihara A, Ramalho JS, Hume AN, Seabra MC (2011) Rab27a targeting to melanosomes requires nucleotide exchange but not effector binding. Traffic 12:1056–1066
Evans RD, Robinson C, Briggs DA, Tooth DJ, Ramalho JS, Cantero M, Montoliu L, Patel S, Sviderskaya EV, Hume AN (2014) Myosin-Va and dynamic actin oppose microtubules to drive long-range organelle transport. Curr Biol 24:1743–1750
Gilboa L, Nohe A, Geissendorfer T, Sebald W, Henis YI, Knaus P (2000) Bone morphogenetic protein receptor complexes on the surface of live cells: a new oligomerization mode for serine/threonine kinase receptors. Mol Biol Cell 11:1023–1035
Chen D, Zhao M, Mundy GR (2004) Bone morphogenetic proteins. Growth Factors 22:233–241
Yaar M, Park HY (2012) Melanocytes: a window into the nervous system. J Invest Dermatol 132:835–845
Bilodeau ML, Greulich JD, Hullinger RL, Bertolotto C, Ballotti R, Andrisani OM (2001) BMP-2 stimulates tyrosinase gene expression and melanogenesis in differentiated melanocytes. Pigment Cell Res 14:328–336
Zhang M et al (2014) BMP-2 overexpression augments vascular smooth muscle cell motility by upregulating myosin va via Erk signaling. Oxidative Med Cell Longev 2014:294150
Hwang JS (2016) Inhibitory effect of 2-methyl-naphtho[1,2,3-de]quinolin-8-one on melanosome transport and skin pigmentation. Sci Rep 6:29189
Zhang M, Yang M, Liu LP, Lau WB, Gao H, Xin MK, Su LX, Wang J, Cheng SJ, Fan Q, Liu JH (2014) BMP-2 overexpression augments vascular smooth muscle cell motility by upregulating myosin Va via Erk signaling. Oxid. Med. Cell. Longey. 2014, 291450
Zawel L, Dai JL, Buckhaults P, Zhou S, Kinzler KW, Vogelstein B, Kern SE (1998) Human Smad3 and Smad4 are sequence-specific transcription activators. Mol Cell Biol 1:611–617
Shi Y, Wang YF, Jayaraman L, Yang H, Massague J, Pavletich NP (1998) Crystal structure of a smad MH1 domain bound to DNA: insights on DNA binding in TGF-beta signaling. Cell 94:585–594
Acknowledgements
This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HP23C0001).
Funding
This research received no external funding.
Author information
Authors and Affiliations
Contributions
Conceptualization, JS.H and JY.P; methodology, JY.P and CS.J; formal analysis, JY.P; investigation, JY.P; resources, JY.P and CH. K; data curation, CS.J and JY.P; writing—original draft preparation, JY.P; writing—review and editing, CS.J; supervision, JS.H; All authors have read and agreed to the published version of the manuscript.
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing interests.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Park, J.Y., Jo, C.S., Ku, C. et al. BMP-2 regulates the expression of myosin Va via smad in melan-a melanocyte. Arch Dermatol Res 316, 225 (2024). https://doi.org/10.1007/s00403-024-02955-9
Received:
Revised:
Accepted:
Published:
DOI: https://doi.org/10.1007/s00403-024-02955-9