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open access eISSN 2093-3673

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Original Article

Anat Cell Biol 2022; 55(2): 190-204

Published online June 30, 2022


Copyright © Korean Association of ANATOMISTS.

Antimicrobial peptide nisin induces spherical distribution of macropinocytosis-like cytokeratin 5 and cytokeratin 17 following immediate derangement of the cell membrane

Norio Kitagawa1,2,3,4

1Oral Medicine Research Center, Fukuoka Gakuen, Fukuoka, 2Department of Dental Hygienist, Fukuoka College of Health Sciences, Fukuoka, 3Department of Morphological Biology, Fukuoka Dental College, Fukuoka, 4Wellbeing Laboratory, Fukuoka, Japan

Correspondence to:Norio Kitagawa
Oral Medicine Research Center, Fukuoka Gakuen, Fukuoka 814-0193, Japan
E-mail: kitagawan@kyudai.jp

Received: August 22, 2021; Revised: October 16, 2021; Accepted: October 19, 2021

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


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 µm 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: Aging, Nisin, Pinocytosis, Keratin-5, Keratin-17

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