Project Details
Projekt
Kindlins and Rho GTPase-mediated signaling pathways
Subject Area
Dermatology
Term
from 2010 to 2014
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 182499804
This project deals with the proteins kindlin-1 and kindlin-2, components of focal adhesions in cells. Kindlin-1, an epithelial specific protein, is medically relevant since mutations in its gene FERMT1 (KIND1) cause the human disease Kindler syndrome (KS; OMIM 173650). Kindlin- 2 is considered to be ubiquitously expressed, but so far no human disease is known to be associated with its genetic defects. Both kindlins are expressed in epidermal keratinocytes, but their specific roles have not been delineated. The KS phenotype with progressive skin and mucosal fragility, photosensitivity, extensive skin atrophy and increased risk of mucocutaneous malignancy offers an excellent model to study the role of focal adhesions in vitro and in the skin in vivo. The goal of this project is to improve our understanding of functional roles of kindlin-1 and -2 in the skin, particularly related to their role in Rho GTPase signaling. Specifically, we aim to define: 1) distinct functions of kindlin-1 and -2 in keratinocytes and fibroblasts; 2) the role of kindlin-1 and -2 in the regulation of Rho GTPases; 3) the implication of Rho GTPases in the pathogenesis of the skin atrophy and premature aging in KS. New knowledge generated by these studies will deliver highly relevant novel information on molecular functions of kindlins and kindlin-mediated signalling and serve as a prerequisite for future development of molecular therapies for rare genetic diseases, but by analogy also for common conditions such as skin atrophy, aging, photosensitivity and carcinogenesis.
DFG Programme
Research Grants
