Loss-of-function FERMT1 mutations in kindler syndrome implicate a role for fermitin family homolog-1 in integrin activation.

[kindler syndrome]

Kindler syndrome is an autosomal recessive disorder characterized by skin atrophy and blistering . It results from loss -of-function mutations in the FERMT 1 gene encoding the focal adhesion protein , fermitin family homolog-1 . How and why deficiency of fermitin family homolog-1 results in skin atrophy and blistering are unclear . In this study , we investigated the epidermal basement membrane and keratinocyte biology abnormalities in Kindler syndrome . We identified altered distribution of several basement membrane proteins , including types IV , VII , and XVII collagens and laminin-332 in Kindler syndrome skin . In addition , reduced immunolabeling intensity of epidermal cell markers such as beta 1 and alpha 6 integrins and cytokeratin 15 was noted . At the cellular level , there was loss of beta 4 integrin immunolocalization and random distribution of laminin-332 in Kindler syndrome keratinocytes . Of note , active beta 1 integrin was reduced but overexpression of fermitin family homolog-1 restored integrin activation and partially rescued the Kindler syndrome cellular phenotype . This study provides evidence that fermitin family homolog-1 is implicated in integrin activation and demonstrates that lack of this protein leads to pathological changes beyond focal adhesions , with disruption of several hemidesmosomal components and reduced expression of keratinocyte stem cell markers . These findings collectively provide novel data on the role of fermitin family homolog-1 in skin and further insight into the pathophysiology of Kindler syndrome .

Diseases
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Diseases presenting "altered distribution of several basement membrane proteins" symptom

kindler syndrome

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