title: The kindlin family: functions, signaling properties and implications for human disease.
abstract: The kindlin (or fermitin) family of proteins comprises three members (kindlin-1,-2 and -3) of evolutionarily conserved focal adhesion (FA) proteins, whose best-known task is to increase integrin affinity for a ligand (also referred as integrin activation) through binding of β-integrin tails. The consequence of kindlin-mediated integrin activation and integrin-ligand binding is cell adhesion, spreading and migration, assembly of the extracellular matrix (ECM), cell survival, proliferation and differentiation. Another hallmark of kindlins is their involvement in disease. Mutations in the KINDLIN-1 (also known as FERMT1) gene cause Kindler syndrome (KS)--in which mainly skin and intestine are affected, whereas mutations in the KINDLIN-3 (also known as FERMT3) gene cause leukocyte adhesion deficiency type III (LAD III), which is characterized by impaired extravasation of blood effector cells and severe, spontaneous bleedings. Also, aberrant expression of kindlins in various forms of cancer and in tissue fibrosis has been reported. Although the malfunctioning of integrins represent a major cause leading to kindlin-associated diseases, increasing evidence also point to integrin-independent functions of kindlins that play an important role in the pathogenesis of certain disease aspects. Furthermore, isoform-specific kindlin functions have been discovered, explaining, for example, why loss of kindlins differentially affects tissue stem cell homeostasis or tumor development. This Commentary focuses on new and isoform-specific kindlin functions in different tissues and discusses their potential role in disease development and progression.
authors.affiliation: Max Planck Institute of Biochemistry, Martinsried 82152, Germany.
authors.forename: Emanuel
authors.initials: E
authors.lastname: Rognoni
authors.affiliation: Max Planck Institute of Biochemistry, Martinsried 82152, Germany.
authors.forename: Raphael
authors.initials: R
authors.lastname: Ruppert
authors.affiliation: Max Planck Institute of Biochemistry, Martinsried 82152, Germany faessler@biochem.mpg.de.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Fässler
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism*; D004194:Disease; D006801:Humans; D008954:Models, Biological; D005810:Multigene Family; D011485:Protein Binding; D015398:Signal Transduction
chemical_list: D002352:Carrier Proteins
keywords: Disease; Integrins; Kindlins