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

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.

Positive Promoting Effects of Smilax China Flower Absolute on the Wound Healing/Skin Barrier Repair‐Related Responses of HaCaT Human Skin Keratinocytes

“…It has been shown downregulation of the Erk1/2 signal reduces keratinocyte migration and proliferation, [36,37] and that increased Erk1/2 phosphorylation is positively associated with keratinocyte migration and proliferation [24,34] . p38 MAPK phosphorylation has also been reported to mediate keratinocyte proliferation and migration [25,38] . On the other hand, JNK signaling was reported to be non‐critical for keratinocyte migration and proliferation [25,39] .…”

Removal of ammonium‐nitrogen from aqueous solution using chitosan‐coated bentonite: Mechanism and effect of operating parameters

“…In the CCB spectra before adsorption, the characteristics peaks of bentonite are the following: 3624.28 cm −1 for inner OH stretching, 3387.23 cm −1 for OH molecules stretching vibrations from water, 1633.19 cm −1 for OH molecules bending vibrations, 1024.00 cm −1 for SiOSi stretching deformation, and 790.64 cm −1 for (Al, Mg) OH vibration modes . The following peaks are attributed to chitosan: 3387.23 cm −1 for NH and OH stretching vibration, 2904.68 cm −1 for CH stretching vibration, and 1633.19 cm −1 for NH bending vibrations …”

MAP4 as a New Candidate in Cardiovascular Disease

“…Microtubule-associated protein 4 is reported to be widely expressed in non-neuronal cells and tissues, such as the adrenal gland, liver, lung, heart, vascular tissues, and skin ( Parysek et al, 1985 ; Kotani et al, 1988 ; Matsushima et al, 2005 ; Hu et al, 2010 ; Li et al, 2015 ; Xia and He, 2018 ; Zhang et al, 2019a ).…”

“…Microtubules, the major component of the cytoskeleton, are composed of α/β tubulin dimers and exhibit a crucial role in regulating many processes, including cell survival and death, cell migration and proliferation, cell shape maintenance, and organelle transport ( Walczak, 2000 ; Birukova et al, 2004 ; Hu et al, 2010 ; Zhang et al, 2013 , 2019a ). In particular, MTs target focal adhesions to regulate extracellular matrix adhesion, and the attachment of MTs to special cortical regions of cells is required for cell polarization ( Small et al, 2002 ).…”