The novel protein kindlin-1 and molecular mechanisms of Kindler syndrome

• Applicant: Professorin Dr. Cristina Has
• Subject Area: Dermatology
• Term: from 2008 to 2013
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 73687317

This project deals with the novel protein kindlin-1, a component of focal adhesions in epithelial cells, and the molecular basis and phenotypic manifestations in Kindler syndrome (KS; OMIM 173650). KS is a heritable skin disorder caused by mutations in the kindlin-1 gene, KIND1, and has an intriguing, evolving phenotype: congenital skin blistering and photosensitivity, which improve with age, and progressive generalized poikiloderma with extensive skin atrophy and increased risk of mucocutaneous malignancy. The research on the molecular mechanisms of KS has high relevance since it will deliver new indirect information on the normal role of kindlin-1 and focal adhesions. Moreover, due to phenotypic similarity with other conditions, KS skin and cells will constitute optimal research models for other pathological phenomena, such as (premature) aging, tissue atrophies, photosensitivity and carcinogenesis. In this project our goal is to establish the functional role of kindlin-1 in the skin and related epithelia and to shed light onto molecular etiopathology of KS. Specifically, we aim to define: 1) the role of kindlin-1 in the epidermis; 2) its phosphorylation and regulation; 3) its ligand interactions; 4) the role of kindlin-1 in outside-in-signalling; 5) expression and functions of its isoforms; and to 6) identify new KIND1 mutations and investigate their phenotypic consequences; and to 7) assess the role of kindlin-1 in acquired pathological processes. New knowledge generated by these studies will contribute to better understanding of epithelial cell biology and serve as a prerequisite for future development of molecular therapies.

• DFG Programme: Research Grants
• Participating Person: Professorin Dr. Leena Kaarina Bruckner-Tuderman