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

First Author  Wang F Year  2018
Journal  J Cell Biol Volume  217
Issue  12 Pages  4314-4330
PubMed ID  30389720 Mgi Jnum  J:269301
Mgi Id  MGI:6259508 Doi  10.1083/jcb.201712130
Citation  Wang F, et al. (2018) Keratin 6 regulates collective keratinocyte migration by altering cell-cell and cell-matrix adhesion. J Cell Biol 217(12):4314-4330
abstractText  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 Krt6a/Krt6b-null keratinocytes, and that inhibiting myosin ATPase activity normalizes the enhanced migration potential of Krt6a/Krt6b-null cells. Desmoplakin, which mediates attachment of IFs to desmosomes, is also expressed at reduced levels and is mislocalized to the nucleus in Krt6a/Krt6b-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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