Flightless I, a contributing factor to skin blistering in Kindler syndrome patients?

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dc.contributor.authorKopecki, Z.
dc.contributor.authorHas, C.
dc.contributor.authorYang, G.
dc.contributor.authorBruckner-Tuderman, L.
dc.contributor.authorCowin, A.
dc.date.issued2020
dc.description.abstractFlii and Kindler syndrome Research Association - Australia. All authors contributed to manuscript preparation and have approved the final submitted and published versions.Kindler syndrome is the autosomal recessive skin disorder characterized by congenital blistering, photo sensitivity and mutations is the FERMT1 gene encoding the focal adhesion protein Kindlin-1 (1) . Kindlin-1 is an integrin binding protein which links integrins to the F-actin cytoskeleton andregulates their activity. Loss of Kindlin-1 results in basement membrane splitting, inflammatory response and development of blistering (2). This impairs the adhesion of basal keratinocytes to the extracellular matrix leading to modifications of the cortical actin network and increased plasticity of the plasma membrane (2). Recent studies have shown that Kindlin-1 regulates epidermal growth factor receptor (EGRF) signalling and protects the receptor from lysosomal-mediated degradation with Kindler syndrome patients having reduced EGRF signalling, leading to defective cell migration and wound re-epithelialisation. Mechanistic studies using a transgenic mouse lacking Kindlin-1 in the epidermis have identified a role for Kindlin-1 in distinct pathways controlling Wnt and TGF-β availability (3). Kindlin-1 regulates stem cell proliferation and cancer development independently of β-integrin signalling (3) ; however the mechanism behind its regulation of the cytoskeleton has not been fully elucidated. Here we describe a link between Kindlin-1 and the actin remodelling protein Flightless I (Flii) which may contribute to the excessive blistering observed in Kindler syndromepatients.
dc.description.statementofresponsibilityZlatko Kopecki, Cristina Has, Gink Yang, Leena Bruckner‐Tuderman, Allison Cowin
dc.identifier.citationJournal of Cutaneous Pathology, 2020; 47(2):186-189
dc.identifier.doi10.1111/cup.13597
dc.identifier.issn0303-6987
dc.identifier.issn1600-0560
dc.identifier.orcidKopecki, Z. [0000-0002-8072-4222]
dc.identifier.orcidCowin, A. [0000-0003-2885-2080]
dc.identifier.urihttp://hdl.handle.net/2440/122456
dc.language.isoen
dc.publisherWiley
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/GNT1102617
dc.rights© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
dc.source.urihttps://doi.org/10.1111/cup.13597
dc.subjectFlightless I
dc.subjectFlii
dc.subjectKindler syndrome
dc.subjectskin blistering
dc.titleFlightless I, a contributing factor to skin blistering in Kindler syndrome patients?
dc.typeJournal article
pubs.publication-statusPublished

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