Faculty Collaboration Database

The integrin co-activator Kindlin-3 is expressed and functional in a non-hematopoietic cell, the endothelial cell. J Biol Chem 2010 Jun 11;285(24):18640-9

Date

04/10/2010

Pubmed ID

20378539

Pubmed Central ID

PMC2881789

DOI

10.1074/jbc.M109.085746

Scopus ID

2-s2.0-77953317401 (requires institutional sign-in at Scopus site)   83 Citations

Abstract

Integrin activation is crucial for numerous cellular responses, including cell adhesion, migration, and survival. Recent studies in mice have specifically emphasized the vital role of kindlin-3 in integrin activation. Kindlin-3 deficiency in humans also has now been documented and includes symptoms of bleeding, frequent infections, and osteopetrosis, which are consequences of an inability to activate beta1, beta2, and beta3 integrins. To date, kindlin-3 was thought to be restricted to hematopoietic cells. In this article, we demonstrate that kindlin-3 is present in human endothelial cells derived from various anatomical origins. The mRNA and protein for KINDLIN-3 was detected in endothelial cells by reverse transcription-PCR and Western blots. When subjected to sequencing by mass spectrometry, the protein was identified as authentic kindlin-3 and unequivocally distinguished from KINDLIN-1 and KINDLIN-2 or any other known protein. By quantitative real time PCR, the level of kindlin-3 in endothelial cells was 20-50% of that of kindlin-2. Using knockdown approaches, we show that kindlin-3 plays a role in integrin-mediated adhesion of endothelial cells. This function depends upon the integrin and substrate and is distinct from that of kindlin-2. Formation of tube-like structures in Matrigel also was impaired by kindlin-3 knockdown. Mechanistically, the distinct functions of the kindlins can be traced to differences in their subcellular localization in integrin-containing adhesion structures. Thus, the prevailing view that individual kindlins exert their functions in a cell type-specific manner must now be modified to consider distinct functions of the different family members within the same cell type.

Author List

Bialkowska K, Ma YQ, Bledzka K, Sossey-Alaoui K, Izem L, Zhang X, Malinin N, Qin J, Byzova T, Plow EF

Author

Yan-Qing Ma PhD Associate Investigator in the Blood Research Institute department at BloodCenter of Wisconsin

MESH terms used to index this publication - Major topics in bold

Blood Platelets
Blotting, Western
Cell Adhesion
Cell Survival
DNA, Complementary
Endothelial Cells
Gene Expression Regulation
Hematopoietic Stem Cells
Humans
Mass Spectrometry
Membrane Proteins
Neoplasm Proteins
RNA, Messenger
Reverse Transcriptase Polymerase Chain Reaction