Kindling the flame of integrin activation and function with kindlins.
OBJECTIVE
There are three kindlin family members in vertebrates, which have high-sequence homology and a common organization signature with a C-terminal 4.1, ezrin, radixin, moesin (FERM) domain bisected by a pleckstrin-homology domain. Although the cell and tissue distributions of the three kindlins differ, there is a consistent and close interrelationship between kindlins and integrins, and alterations of kindlin expression affect integrin-dependent functions. However, in-vivo data on the functions of the kindlins and their mechanisms of action have been lacking.


RESULTS
Recent studies have shown that deficiencies of each of the three kindlins result in profound and distinct phenotypes, ranging from skin and intestinal defects (kindlin-1), embryonic lethality due to cardiac developmental problems (kindlin-2), to marked abnormalities in platelet, leukocyte and erythrocyte function (kindlin-3). A human disease characterized by bleeding, frequent infections and osteopetrosis has now been attributed to mutations in the gene encoding for kindlin-3. These defects are consistent with recent data showing that kindlins control integrin activation and function.


CONCLUSIONS
The three members of the kindlin family have now been implicated as essential regulators of integrin function in individual cells and in whole organisms.
Plow
Edward F
EF
Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, OH 44195, USA. plowe@ccf.org
Qin
Jun
J
Byzova
Tatiana
T
D000818:Animals; D003598:Cytoskeletal Proteins / Q000172:deficiency / Q000502:physiology*; D006801:Humans; D016023:Integrins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D008565:Membrane Proteins / Q000172:deficiency / Q000502:physiology; D009363:Neoplasm Proteins / Q000172:deficiency / Q000502:physiology
D003598:Cytoskeletal Proteins; C475301:FERMT1 protein, human; C477322:FERMT3 protein, human; D016023:Integrins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; C527818:kindlin-3 protein, mouse