Mechanically activated integrin switch controls a5b1 function (Science, 2009, 323:642-644)

報告日期: 2009/03/31
報告時間: 15:10/16:00
報告學生: 張耀宗
講評老師: 吳佳慶
附件下載:

http://basicmed.med.ncku.edu.tw/admin/up_img/980331-1.pdf

http://basicmed.med.ncku.edu.tw/admin/up_img/980331-1Supp.pdf

Mechanically Activated Integrin Switch Controls a5β1 Function

Science. 2009 Jan 30;323(5914):642-4

 

Speaker: 張耀宗

Commentator: 吳佳慶 老師

Date:3/31/2009 pm3:10-4:00

Place:602教室

 

Abstract

The living cell can respond to both chemical and physical environmental signals. It can change the morphology, dynamics, behavior and, eventually, fate by sense and analyze these information. Membrane receptors, present on cells from all organisms that have been examined, undergo conformational transitions in response to foreign force. Integrins, as the main receptors that connect the cytoskeleton to the extracellular matrix (ECM), have a role in the sensing and processing of external mechanical force, such as substrate stretching and fluid shear flow. Application of a force vertical to the membrane triggers conversion of low-affinity integrins to a high-affinity state, which induces new and stable binding to the extracellular matrix. These reinforcement mechanisms can also control the activity of focal adhesion kinase (FAK). The roles of FAK are mediating downstream signaling functions of integrin b subunit and controlling cytoskeletal dynamics. However, there are no ideas about how the mechanical properties of the cell’s microenvironment are transmitted from cell surface receptor to intracellular signal pathways. Friedland et al. provided evidence that the major fibronectin-binding integrin, α5β1, could switch between relaxed and tensioned states and regulated the FAK activity in respond to cytoskeletal force and matrix stiffness. They thought that the external force was required for the conversion of the adhesion bond from a non–cross-linkable to a cross-linkable state and supposed that this change was due to the difference of the binding interface. It is well-known that Integrin α5β1 can recognize two sites in fibronectin: an Arg-Gly-Asp (RGD) sequence in the 10th type III repeat and a secondary synergy site in the 9th repeat. Friedland et al. also showed that conversion to the cross-linkable state required the synergy site and these events were correlated with the phosphorylation of FAK. This environmental signal directly controlled the a5b1-fibronectin bond strength via the synergy site in fibronectin and was required to generate signals by the phosphorylation of focal adhesion kinase.

 

Reference

1.   Geiger B, Spatz JP, Bershadsky AD, Environmental sensing through focal adhesions. Nat Rev Mol Cell Biol. 2009,10(1):21-33.

2.   Bershadsky A, Kozlov M, Geiger B. Adhesion-mediated mechanosensitivity a time to experiment, and a time to theorize. Current Opinion in Cell Biology 2006, 18:472–481