Mechanisms involved in alpha6beta1-integrin-mediated Ca(2+) signalling
H Schöttelndreier1, B V Potter, G W Mayr
1Institute for Medical Biochemistry and Molecular Biology, Division of Cellular Signal Transduction, University of Hamburg, University Hospital Eppendorf, Martinistr. 52, D-20246, Hamburg, Germany.
Cellular Signalling
|December 1, 2001
Summary
Laminin contact triggers sustained calcium (Ca2+) signaling in T-lymphocytes via alpha6beta1-integrin. This involves calcium release and entry, mediated by src kinases and second messengers like InsP3 and cADPR.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- The extracellular matrix (ECM) plays a crucial role in regulating cell behavior.
- Integrins are key mediators of cell-ECM interactions.
- Calcium signaling is fundamental to T-lymphocyte activation and function.
Purpose of the Study:
- To investigate the signaling pathways initiated by T-lymphocyte contact with laminin, an ECM protein.
- To elucidate the role of alpha6beta1-integrin in mediating calcium (Ca2+) signaling.
- To identify the intracellular components involved in this signaling cascade.
Main Methods:
- Jurkat T-lymphocytes were cultured and stimulated with laminin.
- Calcium mobilization was measured using fluorescent indicators.
- Pharmacological inhibitors targeting specific signaling molecules (e.g., src kinase inhibitor PP2, PLC inhibitor U73122, cADPR antagonist 7-deaza-8-Br-cADPR) were employed.
- Thapsigargin was used to assess calcium stores.
Main Results:
- Laminin engagement with Jurkat T-lymphocytes induced long-lasting alpha6beta1-integrin-mediated Ca2+ signaling.
- This signaling involved Ca2+ release from thapsigargin-sensitive stores and capacitative Ca2+ entry through SKF 96365-sensitive channels.
- Inhibition studies revealed the involvement of src tyrosine kinases, phospholipase C (PLC), D-myo-inositol 1,4,5-trisphosphate (InsP3), and cyclic adenosine diphosphoribose (cADPR).
Conclusions:
- Alpha6beta1-integrin-mediated interaction with laminin triggers a complex intracellular calcium signaling pathway in T-lymphocytes.
- Src tyrosine kinases, InsP3, and cADPR are critical components of this signaling cascade.
- Understanding this pathway provides insights into T-lymphocyte activation and adhesion processes.
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