Cell Migration - Polarity in Migrating Cells

Polarity in Migrating Cells

Migrating cells have a polarity—a front and a back. Without it, they would move in all directions at once, i.e. spread. How this arrow is formulated at a molecular level inside a cell is unknown. In a cell that is meandering in a random way, the front can easily give way to become passive as some other region, or regions, of the cell form(s) a new front. In chemotaxing cells, the stability of the front appears enhanced as the cell advances toward a higher concentration of the stimulating chemical. This polarity is reflected at a molecular level by a restriction of certain molecules to particular regions of the inner cell surface. Thus, the phospholipid PIP3 and activated Rac and CDC42 are found at the front of the cell, whereas Rho GTPase and PTEN are found toward the rear.

It is believed that filamentous actins and microtubules are important for establishing and maintaining a cell’s polarity. Drugs that destroy actin filaments have multiple and complex effects, reflecting the wide role that these filaments play in many cell processes. It may be that, as part of the locomotory process, membrane vesicles are transported along these filaments to the cell’s front. In chemotaxing cells, the increased persistence of migration toward the target may result from an increased stability of the arrangement of the filamentous structures inside the cell and determine its polarity. In turn, these filamentous structures may be arranged inside the cell according to how molecules like PIP3 and PTEN are arranged on the inner cell surface. And where these are located appears in turn to be determined by the chemoattractant signals as these impinge on specific receptors on the cell’s outer surface.

Although microtubules have been known to influence cell migration for many years, the mechanism by which they do so has remained controversial. It was recently found that microtubules are not needed for the movement, but they are required to provide directionality to cell movement. When present, microtubules retard cell movement when their dynamics are suppressed by drug treatment or by tubulin mutations. Suppressing dynamics mainly affects the microtubules in the trailing edge of cells and thereby prevents tail retraction.