Tropomyosin Regulates Cell Migration during Skin Wound Healing

Lees, Justin G.; Ching, Yu Wooi; Adams, Damian; Bach, Cuc T.; Samuel, Michael S.; Kee, Anthony J.; Hardeman, Edna C.; Gunning, Peter W.; Cowin, Allison J.; O’Neill, Geraldine M.

doi:10.1038/jid.2012.489

Cited by 45 publications

(42 citation statements)

References 39 publications

(70 reference statements)

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“…Changed expression levels of the different tropomyosin isoforms may therefore coordinate actin and adhesion dynamics to generate discrete migration outcomes. The synchronizing effects of Tm5NM1 on focal adhesion and actin filament stability are in line with the in vivo role we have described for Tm5NM1 during skin wound healing (34). Wound healing is a precisely orchestrated series of timed migration events that are necessary for efficient wound closure.…”

Section: Discussionsupporting

confidence: 49%

“…As we have reported previously, the loss of Tm5NM1 expression induced increased formation of focal complexes, contrasting with the loss of focal complexes in cells with high-level Tm5NM1 expression (Fig. 2C) (4,34). Assessment of Src kinase activity by an in vitro kinase activity assay reveals ϳ2-fold-higher activity in Tm5NM1…”

Section: Resultsmentioning

confidence: 69%

“…Next, we asked whether the reduced rate of Y527FSrc delivery to focal adhesions results in decreased phosphorylation of focal-adhesion-localized substrate molecules. We have shown previously that levels of phosphorylated paxillin are inversely correlated with Tm5NM1 expression (4,34). To explicitly assess the relationship between Tm5NM1 expression and Src-mediated phosphorylation of substrates at focal adhesions, Src/Yes/Fyn Ϫ/Ϫ MEFs were reconstituted with exogenous GFP-tagged Src together with CFP-tagged Tm5NM1.…”

Section: Resultsmentioning

confidence: 99%

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Tropomyosin Tm5NM1 Spatially Restricts Src Kinase Activity through Perturbation of Rab11 Vesicle Trafficking

Bach

Murray

Owen

et al. 2014

Molecular and Cellular Biology

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dIn order for cells to stop moving, they must synchronously stabilize actin filaments and their associated focal adhesions. How these two structures are coordinated in time and space is not known. We show here that the actin association protein Tm5NM1, which induces stable actin filaments, concurrently suppresses the trafficking of focal-adhesion-regulatory molecules. Using combinations of fluorescent biosensors and fluorescence recovery after photobleaching (FRAP), we demonstrate that Tm5NM1 reduces the level of delivery of Src kinase to focal adhesions, resulting in reduced phosphorylation of adhesion-resident Src substrates. Live imaging of Rab11-positive recycling endosomes that carry Src to focal adhesions reveals disruption of this pathway. We propose that tropomyosin synchronizes adhesion dynamics with the cytoskeleton by regulating actin-dependent trafficking of essential focal-adhesion molecules. Cell migration is essential for normal embryonic development, wound healing, and immune response, and migration dysregulation underpins an array of pathological conditions. Much focus is given to the initiation and speed of migration; however, of equal importance are the mechanisms by which migration is arrested. Integrin-based focal adhesions, which are bound on the external surface to the extracellular matrix and internally to the actin cytoskeleton, are key structural elements of the machinery that drives cell migration (1). While actin filament stabilization inhibits cell migration (2-6), little is known about how the associated focal adhesions are synchronously stabilized along with actin filaments. This is critical, because events that trigger focal adhesion disassembly correspondingly break the adhesion-cytoskeleton linkage (7-9), facilitating new cycles of membrane protrusion and forward movement (10). Thus, in order to stop migrating, cells must have mechanisms to synchronize actin and adhesion stability.The tropomyosins are a multi-isoform family of actin-binding proteins that display spatially and temporally restricted association with discrete actin filament populations (11). Dimers of tropomyosin associate head to tail, forming a coiled polymer that lies in the major groove of the actin filament. The association of discrete tropomyosin isoforms is thought to regulate the dynamic state of actin filaments by affecting the association of other actinregulatory proteins (12). Thus, cells with altered tropomyosin expression profiles display differential actin filament stability (2, 4, 13). Moreover, tropomyosin isoform expression is correlated with different focal-adhesion morphology (4, 14) and isoform-specific effects on cell migration (2, 4, 14-16). The tropomyosin isoform Tm5NM1 is ubiquitously expressed (17), and elevated expression inhibits both 2-dimensional (2D) (2, 4) and 3D (16) cell migration. In line with these migration effects, Tm5NM1 induces actin filament stability (13) coupled with highly stabilized focal adhesions (4).Tm5NM1-mediated actin filament stabilization is accompanied by reduce...

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Section: Discussionsupporting

confidence: 49%

Section: Resultsmentioning

confidence: 69%

Section: Resultsmentioning

confidence: 99%

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Tropomyosin Tm5NM1 Spatially Restricts Src Kinase Activity through Perturbation of Rab11 Vesicle Trafficking

Bach

Murray

Owen

et al. 2014

Molecular and Cellular Biology

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“…Tropomyosin is a multi-isoform family of actin-associating proteins that controls isoform-specific regulation of diverse actin filaments (Bach et al, 2009;Gunning et al, 2005). A recent report by Lees et al (2013) suggested that the tropomyosin may be important regulators of actin functioning during the wound healing process. In short, actin, myosin and tropomysosin are directly involved in the regulation and maintenance of wound recovery.…”

Section: Actin Myosin and Tropomyosinmentioning

confidence: 99%

Proteomic Profiling of Freeze- and Spray-Dried Water Extracts of Snakehead Fish (Channa striatus): In Search of Biomolecules for Wound Healing Properties

Kwan¹,

Baie²,

Mohammed³

et al. 2015

S. Asian J. Life Sci.

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| Channa striatus is a carnivorous freshwater fish that is commonly consumed among Malaysians. The fish is known to contain compound(s) that can accelerate the wound healing process in humans, but the attributes of these compound(s) are yet to be clarified. In the current study, we have performed a thorough proteomic profiling of spray -dried and freeze-dried C. striatus water extracts using high-sensitivity liquid chromatography tandem mass spectrometry. Other than the analysis of whole sample, both samples were also fractionated in order to maximise protein detection. About 137 and 194 proteins were identified in spray dried and freeze dried samples, respectively. Actin, myosin, tropomyosin, calcium ion-related protein and collagen are among the proteins that have been identified, and which are suspected to be involved in the wound healing process. A high number of uncharacterised proteins were also detected, which suggested that there are still many fish proteins with unknown functions in C. striatus. In the future, the identified proteins can be isolated and further studies are required for a better understanding on the wound healing property of C. striatus.

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“…There is a possibility that some of the proteins identified in BD and SD could be associated with speeding up wound healing. It is interesting to note that some cytoskeletal proteins including actin [148][149][150][151][152], profilin [153,154], alpha tubulin [154], calponin [155,156], nonmuscle myosin [149,157,158], thymosin [159], and tropomyosin [160] identified at high abundance in BD and SD saliva were associated with different aspects of wound healing. Could secretion of these proteins at high abundance be the tick's way to help the host heal?…”

Section: Housekeeping Proteins and Other Tspsmentioning

confidence: 99%

Ixodes scapularistick saliva proteins sequentially secreted every 24h during blood feeding

Kim¹

2016

2016 International Congress of Entomology

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Ixodes scapularis is the most medically important tick species and transmits five of the 14 reportable human tick borne disease (TBD) agents in the USA. This study describes LC-MS/MS identification of 582 tick-and 83 rabbit proteins in saliva of I. scapularis ticks that fed for 24,48,72,96, and 120 h, as well as engorged but not detached (BD), and spontaneously detached (SD). The 582 tick proteins include proteases (5.7%), protease inhibitors (7.4%), unknown function proteins (22%), immunity/antimicrobial (2.6%), lipocalin (3.1%), heme/iron binding (2.6%), extracellular matrix/ cell adhesion (2.2%), oxidant metabolism/ detoxification (6%), transporter/ receptor related (3.2%), cytoskeletal (5.5%), and housekeeping-like (39.7%). Notable observations include: (i) tick saliva proteins of unknown function accounting for >33% of total protein content, (ii) 79% of proteases are metalloproteases, (iii) 13% (76/582) of proteins in this study were found in saliva of other tick species and, (iv) ticks apparently selectively inject functionally similar but unique proteins every 24 h, which we speculate is the tick's antigenic variation equivalent strategy to protect important tick feeding functions from host immune system. The host immune responses to proteins present in 24 h I. scapularis saliva will not be effective at later feeding stages. Rabbit proteins identified in our study suggest the tick's strategic use of host proteins to modulate the feeding site. Notably fibrinogen, which is central to blood clotting and wound healing, was detected in high abundance in BD and SD saliva, when the tick is preparing to terminate feeding and detach from the host. A remarkable tick adaptation is that the feeding lesion is completely healed when the tick detaches from the host. Does the tick concentrate fibrinogen at the feeding site to aide in promoting healing of the feeding lesion? Overall, these data provide broad insight into molecular mechanisms regulating different tick feeding phases. These data set the foundation for in depth I. scapularis tick feeding physiology and TBD transmission studies.PLOS Neglected Tropical Diseases |

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Tropomyosin Regulates Cell Migration during Skin Wound Healing

Cited by 45 publications

References 39 publications

Tropomyosin Tm5NM1 Spatially Restricts Src Kinase Activity through Perturbation of Rab11 Vesicle Trafficking

Tropomyosin Tm5NM1 Spatially Restricts Src Kinase Activity through Perturbation of Rab11 Vesicle Trafficking

Proteomic Profiling of Freeze- and Spray-Dried Water Extracts of Snakehead Fish (Channa striatus): In Search of Biomolecules for Wound Healing Properties

Ixodes scapularistick saliva proteins sequentially secreted every 24h during blood feeding

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