Adhesion and Migration, the Diverse Functions of the Laminin α3 Subunit

Hamill, Kevin J.; Paller, Amy S.; Jones, Jonathan

doi:10.1016/j.det.2009.10.009

Cited by 40 publications

(32 citation statements)

References 79 publications

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“…The molecule increases its adhesive activity upon cleavage of the α3 subunit into a 160 kDa isoform [33]. This mature form of LN332 supports the formation of hemidesmosomes, linking the ECM with the keratin cytoskeleton via the integrin α6β4 [34–36]. The mature LN332 can also support the formation of focal adhesions by binding to the integrin α3β1, which links the ECM to the actin cytoskeleton [37].…”

Section: Discussionmentioning

confidence: 99%

The influence of substrate topography on the migration of corneal epithelial wound borders

et al. 2013

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Currently available artificial corneas can develop post-implant complications including epithelial downgrowth, infection, and stromal melting. The likelihood of developing these disastrous complications could be minimized through improved formation and maintenance of a healthy epithelium covering the implant. We hypothesize that this epithelial formation may be enhanced through the incorporation of native corneal basement membrane biomimetic chemical and physical cues onto the surface of the keratoprosthesis. We fabricated hydrogel substrates molded with topographic features containing specific bio-ligands and developed an in vitro wound healing assay. In our experiments, the rate of corneal epithelial wound healing was significantly increased by 50% in hydrogel surfaces containing topographic features, compared to flat surfaces with the same chemical attributes. We determined that this increased healing is not due to enhanced proliferation or increased spreading of the epithelial cells, but to an increased active migration of the epithelial cells. These results show the potential benefit of restructuring and improving the surface of artificial corneas to enhance epithelial coverage and more rapidly restore the formation of a functional epithelium.

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Section: Discussionmentioning

confidence: 99%

The influence of substrate topography on the migration of corneal epithelial wound borders

et al. 2013

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“…A good example of this is a rare disorder termed laryngo-onycho-cutaneous syndrome (LOC) which presents with non-healing cutaneous erosions and chronic overproduction of granulation tissue without apparent skin fragility [27]. Mutational analyses have revealed that LOC syndrome results from mutations in the first exon of the laminin α3a transcript implicating this region in the regulation of the granulation tissue response [27]. …”

Section: Skin Diseases Involving Hemidesmosomes and Focal Contactsmentioning

confidence: 99%

Hemidesmosomes and focal contact proteins: Functions and cross-talk in keratinocytes, bullous diseases and wound healing

Tsuruta

Hashimoto

Hamill

et al. 2011

Journal of Dermatological Science

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115

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The outer most layer of the skin, the epidermis, is attached to the dermis via a sheet of extracellular matrix proteins termed the basement membrane zone (BMZ). In the intact skin, adhesion of the keratinocytes in the basal layer of the epidermis to the BMZ is facilitated primarily by hemidesmosomes which associate with the keratin cytoskeleton. Cultured keratinocytes do not assemble bona fide hemidesmosomes although hemidesmosome protein clusters (stable anchoring contacts) are found along the substrate-attached surface of the cells and towards the leading edge of keratinocytes repopulating scratch wounds. Actin cytoskeleton-associated matrix adhesion devices termed focal contacts are not thought to play an important role in the adhesion of keratinocytes to the BMZ in intact skin but are prominent in cultured keratinocytes where they are believed to regulate cell migration. We review the molecular components, functions, dynamics and cross-talk of hemidesmosomes and focal contacts in keratinocytes. In addition, we briefly describe what is known about their role in autoimmune and genetic blistering diseases of the skin. We also discuss recent publications which indicate, contrary to expectation, that certain focal contact proteins retard keratinocyte migration while hemidesmosomal proteins regulate directed keratinocyte motility during wound healing.

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“…These changes disrupted the formation and maturation of desmosome junctions. We hypothesized that the global change in RhoA activity may also affect cell–substrate attachments, including integrin-based focal adhesions, as such adhesions are known to regulate cell behavior via functional interactions with small GTPases and the actin cytoskeleton (Hamill et al, 2009; Hamill et al, 2010; Hamill et al, 2011; Tsuruta et al, 2011; Hong et al, 2012). We set out to address the possibility that PKP2 functions to integrate signals within the keratinocyte adhesive network of both cadherin- and integrin-based adhesions.…”

Section: Introductionmentioning

confidence: 99%

Plakophilin 2 Affects Cell Migration by Modulating Focal Adhesion Dynamics and Integrin Protein Expression

Koetsier

Amargo

Todorović

et al. 2014

Journal of Investigative Dermatology

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Plakophilin 2 (PKP2), a desmosome component, modulates the activity and localization of the small GTPase RhoA at sites of cell–cell contact. PKP2 regulates cortical actin rearrangement during junction formation, and its loss is accompanied by an increase in actin stress fibers. We hypothesized that PKP2 may regulate focal adhesion dynamics and cell migration. Here we show that PKP2-deficient cells bind efficiently to the extracellular matrix, but upon spreading display total cell areas ~30% smaller than control cells. Focal adhesions in PKP2-deficient cells are ~2× larger and more stable than in control cells, and vinculin displays an increased time for fluorescence recovery after photobleaching. Furthermore, β4 and β1 integrin protein and mRNA expression is elevated in PKP2-silenced cells. Normal focal adhesion phenotypes can be restored in PKP2-null cells by dampening the RhoA pathway or silencing β1 integrin. However, integrin expression levels are not restored by RhoA signaling inhibition. These data uncover a potential role for PKP2 upstream of β1 integrin and RhoA in integrating cell–cell and cell–substrate contact signaling in basal keratinocytes necessary for the morphogenesis, homeostasis, and reepithelialization of the stratified epidermis.

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Adhesion and Migration, the Diverse Functions of the Laminin α3 Subunit

Cited by 40 publications

References 79 publications

The influence of substrate topography on the migration of corneal epithelial wound borders

The influence of substrate topography on the migration of corneal epithelial wound borders

Hemidesmosomes and focal contact proteins: Functions and cross-talk in keratinocytes, bullous diseases and wound healing

Plakophilin 2 Affects Cell Migration by Modulating Focal Adhesion Dynamics and Integrin Protein Expression

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