Tensegrin in context: Dual role of α8 integrin in the migration of different cell types

Abstract

α8β1 integrin is highly expressed in cells with contractile function, such as mesangial cells of the kidneys and vascular smooth muscle cells (VSMCs). Although it promotes migration of neural crest cells and breast cancer cells, recent studies suggest that α8 integrin has a negative regulatory role in VSMC migration. In this review, the question of why α8β1 integrin plays a dual role in cell migration is raised and discussed. It seems that cells require optimum contractility and balanced tensile forces for migration. α8β1 integrin promotes migration of cells that are initially in a less than optimal contractile state (e.g. neural cells) and reduces the migration of cells known as contractile cells. α8β1 integrin can be called “Tensegrin” as it fits perfectly into the tensegrity model (tensional integrity) and seems to play a prominent role in the integration of the tensile forces.

Figure 1

Contractility and migration. The blue line shows that the cells, which are not initially in the contractile state (1), increase their contractility and approach the optimum level (2) in order to reach their maximum migratory ability. However, contractile cells (3) have maximum migration when their contractility is reduced (red line).

Figure 2

Reduced membrane-associated RhoA after α8 integrin gene silencing. (A) Western blotting analysis showed that α8 gene silencing decreased membrane-associated RhoA (right diagram and blots), while cytosolic RhoA was not significantly changed (left diagram and blots). siRNA-luciferase served as the control for siRNA-α8. Adapted from ref. . (B) Schematic presentation of VSMC phenotype modulation after α8 gene silencing. α8 gene silencing leads to the disassembly of actin stress fibers, and dislocation of RhoA from focal adhesion sites. Actin fibers are shown as red lines and RhoA as purple dots. Left part is before applying siRNA-a8 and right part is after applying siRNA.