Integrin signalling in directed cell migration

Abstract

Migrating cells tend to continue moving in the same direction, a property called persistence. During migration, cells, by definition, form new adhesions at their front and break old adhesions at the rear. We hypothesize that the distinction between new adhesions at the front and older adhesions at the rear plays a major role in directional persistence. We propose specific mechanisms of persistence on the basis of known properties of integrin signals, in hope of stimulating investigation of these ideas.

SLK-mediated phosphorylation of paxillin is required for focal adhesion turnover and cell migration

“…Migratory cells form a stable sub-population of microtubules at the leading edge to reorient the microtubule organizing center (MTOC) between the nucleus and the leading edge to create a polarized microtubule array that directs vesicular trafficking and maintains cell shape [9,10,19]. Additionally, disruption of the microtubule network by nocodazole-induced microtubule catastrophe or taxol-mediated microtubule stabilization, results in a depolarized cell morphology and a dramatic reduction in both the rate and directionality of migration [2,20]. Conversely, release from the stabilizing effects of microtubule antagonists has been shown to induce microtubule regrowth toward the membrane ruffle, activation of Rac1 and the formation of filopodia and lamellipodia [2,19,21].…”

“…Additionally, disruption of the microtubule network by nocodazole-induced microtubule catastrophe or taxol-mediated microtubule stabilization, results in a depolarized cell morphology and a dramatic reduction in both the rate and directionality of migration [2,20]. Conversely, release from the stabilizing effects of microtubule antagonists has been shown to induce microtubule regrowth toward the membrane ruffle, activation of Rac1 and the formation of filopodia and lamellipodia [2,19,21]. lamellipodia, ruffles, filopodia and lamellae.…”

“…For example, nocodazole-induced microtubule depolymerisation leads to an increase in the number and size of focal adhesions at both the leading and trailing edge, anchoring the cell to the ECM to the point where it becomes immobilized [19]. Rescue of microtubule growth following catastrophe shows a resurgence in targeting events of focal adhesions by microtubule plus ends, resulting in focal adhesion dissolution and cell migration [2,19,20]. Microtubule plus ends have been shown to be differentially regulated depending on their subcellular location within the migrating cell.…”

“…Additionally, this may explain why phosphoryl group, it is unlikely that in a heterogeneous population of cells that we would be able to visualize this interaction by Western blot. However, in order to confirm this hypothesis, we must first determine (1) whether SLK is capable of phosphorylating paxillin in vivo and if so, (2) at what point during the onset of migration does this phosphorylation at S250 occur.…”

“…Consequently, cytoskeletal dynamics have been shown to play a critical role in each of the four stages involved in acquiring a migratory phenotype: cellular extension, adhesion, contraction and release [2,7,8,11].…”