2015
DOI: 10.1038/jid.2015.46
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Keratins Stabilize Hemidesmosomes through Regulation of β4-Integrin Turnover

Abstract: Epidermal integrity and wound healing depend on remodeling of cell-matrix contacts including hemidesmosomes. Mutations in β4-integrin and plectin lead to severe epidermolysis bullosa (EB). Whether mutations in keratins K5 or K14, which cause EB simplex, also compromise cell-matrix adhesion through altering hemidesmosomal components is not well investigated. In particular, the dependence of β4-integrin endocytosis and turnover on keratins remains incompletely understood. Here, we show that the absence of kerati… Show more

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Cited by 55 publications
(54 citation statements)
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References 42 publications
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“…We show here that EGF stimulation facilitates proteolytic cleavage of ITGβ4, most likely effecting hemidesmosomal disassembly. In line with previous studies on the intracellular trafficking of ITGβ4, the processed ITGβ4 subunits can be endocytosed and recycled back to the cell surface, with the help of Rab11 and caveolin (Seltmann et al, 2015), to form new adhesive/moving structures. It would therefore be of interest to further investigate the trafficking of ITGβ4 and the effect of LMP2A on this process in NPC cells.…”
Section: Discussionsupporting
confidence: 79%
“…We show here that EGF stimulation facilitates proteolytic cleavage of ITGβ4, most likely effecting hemidesmosomal disassembly. In line with previous studies on the intracellular trafficking of ITGβ4, the processed ITGβ4 subunits can be endocytosed and recycled back to the cell surface, with the help of Rab11 and caveolin (Seltmann et al, 2015), to form new adhesive/moving structures. It would therefore be of interest to further investigate the trafficking of ITGβ4 and the effect of LMP2A on this process in NPC cells.…”
Section: Discussionsupporting
confidence: 79%
“…Our findings deviate from this paradigm in the E0771 mammary cancer model, as depletion of Krtap5-5 not only caused loss of the keratin cytoskeleton but also led to disorganization of the actin cytoskeleton and reduced cell invasion. Our discovery that knockdown of Krtap5-5 or Krt18 affects α6/β4-integrins is supported by others who reported that keratins stabilize hemidesmosomes via their interplay with β4-integrin 44 .…”
Section: Discussionsupporting
confidence: 72%
“…However, it is unknown how the different hemidesmosome components are spatially organized relative to one another. Neither is it known how the keratin intermediate filaments are anchored to hemidesmosomes in cultured keratinocytes, or whether they are directly involved in the organization of the hemidesmosome structure (Song et al, 2015;Seltmann et al, 2015).…”
Section: Introductionmentioning
confidence: 99%