Colocalization of kindlin-1, kindlin-2, and migfilin at keratinocyte focal adhesion and relevance to the pathophysiology of Kindler syndrome.

[kindler syndrome]

Kindler syndrome (KS ) results from pathogenic loss -of-function mutations in the KIND 1 gene , which encodes kindlin-1 , a focal adhesion and actin cytoskeleton-related protein . How and why abnormalities in kindlin-1 disrupt keratinocyte cell biology in KS , however , is not yet known . In this study , we identified two previously unreported binding proteins of kindlin-1 : kindlin-2 and migfilin . Co -immunoprecipitation and confocal microscopy studies show that these three proteins bind to each other and colocalize at focal adhesion in HaCaT cells and normal human keratinocytes . Moreover , loss -of-function mutations in KIND 1 result in marked variability in kindlin-1 immunolabeling in KS skin , which is mirrored by similar changes in kindlin-2 and migfilin immunoreactivity . Kindlin-1 , however , may function independently of kindlin-2 and migfilin , as loss of kindlin-1 expression in HaCaT keratinocytes by RNA interference and in KS keratinocytes does not affect KIND 2 or FBLIM 1 (migfilin ) gene expression or kindlin-2 and migfilin protein localization . In addition to identifying protein-binding partners for kindlin-1 , this study also highlights that KIND 1 gene expression and kindlin-1 protein labeling are not always reduced in KS , findings that are relevant to the accurate laboratory diagnosis of this genodermatosis by skin immunohistochemistry .

Diseases
Validation

Diseases presenting "mutations in the kind1 gene" symptom

kindler syndrome

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