Keratin 6 regulates collective keratinocyte migration by altering cell-cell and cell-matrix adhesion

The a and b isoforms of keratin 6 (K6), a type II intermediate filament (IF) protein, are robustly induced upon injury to interfollicular epidermis. We previously showed that complete loss of K6a/K6b stimulates keratinocyte migration, correlating with enhanced Src activity. In this study, we demonst...

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Published inThe Journal of cell biology Vol. 217; no. 12; pp. 4314 - 4330
Main Authors Wang, Fengrong, Chen, Song, Liu, Hans B, Parent, Carole A, Coulombe, Pierre A
Format Journal Article
LanguageEnglish
Published United States Rockefeller University Press 03.12.2018
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Summary:The a and b isoforms of keratin 6 (K6), a type II intermediate filament (IF) protein, are robustly induced upon injury to interfollicular epidermis. We previously showed that complete loss of K6a/K6b stimulates keratinocyte migration, correlating with enhanced Src activity. In this study, we demonstrate that this property is cell autonomous, depends on the ECM, and results from elevated speed, enhanced directionality, and an increased rate of focal adhesion disassembly. We show that myosin IIA interacts with K6a/K6b, that its levels are markedly reduced in -null keratinocytes, and that inhibiting myosin ATPase activity normalizes the enhanced migration potential of -null cells. Desmoplakin, which mediates attachment of IFs to desmosomes, is also expressed at reduced levels and is mislocalized to the nucleus in -null cells, correlating with defects in cell adhesion. These findings reveal that K6a/K6b modulate keratinocyte migration by regulating cell-matrix and cell-cell adhesion and highlight a role for keratins in collective cell migration.
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ISSN:0021-9525
1540-8140
DOI:10.1083/jcb.201712130