What mechanisms drive retraction of the trailing edge?2018-02-06T10:54:13+00:00

What mechanisms drive retraction of the trailing edge?

Protrusion at the front and retraction at the rear are key force-generating processes at the cell periphery that culminate in the translocation of the cell. For forces to be translated into a net forward gain in cellular movement, the trailing edge must retract as the leading edge protrudes forward. In order for this to occur focal adhesions at the rear of the cell, and the actin filament network to which they are linked, must be disassembled. Prevention of this step would result in the cell being permanently anchored to its substrate.

Prior to retraction of the trailing edge, large-scale actomyosin activity at the rear of the cell reorganizes the cytoskeleton. This alters the actin flow and essentially polarizes the cell to influence the direction it will migrate [1]. The contractile forces generated by the actomyosin network facilitate the retraction of the trailing edge [2][3] via a mechanism similar to that of Myosin Motors and Actin Filament Contractions. Myosin II is a major regulator of this contractility, generating increased tensile forces at the trailing edge and simultaneously relieving tension at the leading edge [4][5]. This ultimately leads to retraction at the rear and extension at the front. Both myosin IIA and IIB are involved in this however each contributes differently. Myosin IIA is important in retraction and adhesion disassembly at the rear of the cell whilst myosin IIB plays a greater role in crosslinking of actin filaments and the establishment of a front-rear polarity [6][7].

Focal adhesion disassembly eases separation of the trailing edge from the underlying substrate in response to the increase in actomyosin contractility. The subsequent retraction of the trailing edge results from the buildup of tensile forces at the rear of the cell which sever the interactions between the cytoskeleton and the cell substrate. These interactions are maintained by integrins however during retraction the integrins will remain attached to the substrate, whilst other components of the FA move towards the cell body and dissipate [8].

Further to the intracellular processes that promote detachment, namely FA disassembly and actomyosin contractility, extracellular events are also speculated to contribute (as reviewed in [9]). Extracellular matrix (ECM) proteases could digest the underlying substrate, whilst sheddases could cleave cell surface proteins bound to the substrate. Together these intracellular and extracellular events free the trailing edge of the cell from the substrate to which it is bound, allowing retraction to occur.

Video. Step Four of Cell Movement: Retraction: Dr. Jim Bear provides a tutorial on the four steps of cell movement. This cell movie shows the fourth step in cell movement - retraction.
Retraction of the trailing edge of a motile cell. This video, on a repeated loop, shows the retraction of the rear of a motile cell. [Video uploaded to YouTube by UNCLineberger.]

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  8. Laukaitis CM, Webb DJ, Donais K, and Horwitz AF. Differential dynamics of alpha 5 integrin, paxillin, and alpha-actinin during formation and disassembly of adhesions in migrating cells. J. Cell Biol. 2001; 153(7):1427-40. [PMID: 11425873]
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