Anatomy and Cell Biology

Korean Association of Anatomists (대한해부학회)
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Antimicrobial peptide nisin induces spherical distribution of macropinocytosis-like cytokeratin 5 and cytokeratin 17 following immediate derangement of the cell membrane

  • Norio Kitagawa (Oral Medicine Research Center, Fukuoka Gakuen)
  • Received : 2021.08.22
  • Accepted : 2021.10.19
  • Published : 2022.06.30
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Abstract

The anti-aging effects of Lactococcus lactis are extensively investigated. Nisin is an antimicrobial peptide produced by L. lactis subsp. lactis. We previously reported that 24-hour nisin treatment disturbs the intermediate filament distribution in human keratinocytes. Additionally, we showed that the ring-like distribution of the intermediate filament proteins, cytokeratin (CK) 5 and CK17 is a marker of nisin action. However, two questions remained unanswered: 1) What do the CK5 and CK17 ring-like distributions indicate? 2) Is nisin ineffective under the experimental conditions wherein CK5 and CK17 do not exhibit a ring-like distribution? Super resolution microscopy revealed that nisin treatment altered CK5 and CK17 distribution, making them spherical rather than ring-like, along with actin incorporation. This spherical distribution was not induced by the suppression of endocytosis. The possibility of a macropinocytosis-like phenomenon was indicated, because the spherical distribution was >1 ㎛ in diameter and the spherical distribution was suppressed by macropinocytosis inhibiting conditions, such as the inclusion of an actin polymerization inhibitor and cell migration. Even when the spherical distribution of CK5 and CK17 was not induced, nisin induced derangement of the cell membrane. Nisin treatment for 30 minutes deranged the regular arrangement of the lipid layer (flip-flop); the transmembrane structure of the CK5-desmosome or CK17-desmosome protein complex was disturbed. To the best of our knowledge, this is the first study to report that CK5 and CK17 in a spherical distribution could be involved in a macropinosome-like structure, under certain conditions of nisin action in keratinocytes.

Keywords

Acknowledgement

This study was supported by JSPS KAKENHI Grants (numbers 15K21564 and 17K18302), the Private University Research Branding Project to Fukuoka College of Health Science from the Ministry of Education, and a grant from the Oral Medicine Research Center of Fukuoka Gakuen.

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