Int J Biol Sci 2019; 15(9):1962-1976. doi:10.7150/ijbs.35440 This issue Cite

Research Paper

Microtubule-associated protein 4 phosphorylation regulates epidermal keratinocyte migration and proliferation

Junhui Zhang1,2*, Lingfei Li1,2*, Qiong Zhang1,2, Wensheng Wang1,2, Dongxia Zhang1,2, Jiezhi Jia1,2, Yanling Lv1,2, Hongping Yuan1,2, Huapei Song1,2, Fei Xiang1,2, Jiongyu Hu1,2,3✉, Yuesheng Huang1,2✉

1. Institute of Burn Research, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
2. State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
3. Endocrinology Department, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
* These authors contributed equally to this work.

Citation:
Zhang J, Li L, Zhang Q, Wang W, Zhang D, Jia J, Lv Y, Yuan H, Song H, Xiang F, Hu J, Huang Y. Microtubule-associated protein 4 phosphorylation regulates epidermal keratinocyte migration and proliferation. Int J Biol Sci 2019; 15(9):1962-1976. doi:10.7150/ijbs.35440. https://www.ijbs.com/v15p1962.htm
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Abstract

Graphic abstract

Both cell migration and proliferation are indispensable parts of reepithelialization during skin wound healing, which is a complex process for which the underlying molecular mechanisms are largely unknown. Here, we identify a novel role for microtubule-associated protein 4 (MAP4), a cytosolic microtubule-binding protein that regulates microtubule dynamics through phosphorylation modification, as a critical regulator of epidermal wound repair. We showed that MAP4 phosphorylation was induced in skin wounds. In an aberrant phosphorylated MAP4 mouse model, hyperphosphorylation of MAP4 (S737 and S760) accelerated keratinocyte migration and proliferation and skin wound healing. Data from both primary cultured keratinocytes and HaCaT cells in vitro revealed the same results. The promigration and proproliferation effects of MAP4 phosphorylation depended on microtubule rearrangement and could be abolished by MAP4 dephosphorylation. We also identified p38/MAPK as an upstream regulator of MAP4 phosphorylation in keratinocytes. Our findings provide new insights into the molecular mechanisms underlying wound-associated keratinocyte migration and proliferation and identify potential targets for the remediation of defective wound healing.

Keywords: keratinocyte, MAP4, phosphorylation, p38/MAPK, migration, proliferation


Citation styles

APA
Zhang, J., Li, L., Zhang, Q., Wang, W., Zhang, D., Jia, J., Lv, Y., Yuan, H., Song, H., Xiang, F., Hu, J., Huang, Y. (2019). Microtubule-associated protein 4 phosphorylation regulates epidermal keratinocyte migration and proliferation. International Journal of Biological Sciences, 15(9), 1962-1976. https://doi.org/10.7150/ijbs.35440.

ACS
Zhang, J.; Li, L.; Zhang, Q.; Wang, W.; Zhang, D.; Jia, J.; Lv, Y.; Yuan, H.; Song, H.; Xiang, F.; Hu, J.; Huang, Y. Microtubule-associated protein 4 phosphorylation regulates epidermal keratinocyte migration and proliferation. Int. J. Biol. Sci. 2019, 15 (9), 1962-1976. DOI: 10.7150/ijbs.35440.

NLM
Zhang J, Li L, Zhang Q, Wang W, Zhang D, Jia J, Lv Y, Yuan H, Song H, Xiang F, Hu J, Huang Y. Microtubule-associated protein 4 phosphorylation regulates epidermal keratinocyte migration and proliferation. Int J Biol Sci 2019; 15(9):1962-1976. doi:10.7150/ijbs.35440. https://www.ijbs.com/v15p1962.htm

CSE
Zhang J, Li L, Zhang Q, Wang W, Zhang D, Jia J, Lv Y, Yuan H, Song H, Xiang F, Hu J, Huang Y. 2019. Microtubule-associated protein 4 phosphorylation regulates epidermal keratinocyte migration and proliferation. Int J Biol Sci. 15(9):1962-1976.

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