Mechanism of cell rear retraction in migrating cells
Section snippets
More than one type of motile force drives cell rear retraction
For myosin II-motor-based cell rear retraction in motile cells [1, 2, 3, 4] there are differences in the way in which motor-based contractile force is generated (Figure 1a–c), but for all migrating cells so far tested classic contraction-force similar to muscle sarcomeres is the least abundant [5, 6] (Figure 1a). This is due to key differences in actin filament organisation discovered in migrating cells which have the wrong actin filament polarity to allow sarcomeric-type contraction force
Force from cell protrusion drags the cell rear forwards
One earlier idea [1] to explain why in some cells, myosin II-motor-based contractility could only account for some of the motile force needed to retract the cell rear was that force from cell protrusion contributes to pulling the cell rear forwards. In other words the cell rear is a passive passenger pulled along by a protruding cell front. A recent careful study has provided direct evidence for such a model in migrating whole keratocytes [23••]. Inhibition of myosin II-contractility either
Actin filament depolymerisation-based and actin filament crosslinking-based contraction directly pulls the cell rear forwards
In nematode worm sperm cells, which lack actin and cytoskeletal motor proteins, retraction of the cell rear and cell body is instead driven by contractile force derived from either depolymerisation of MSP polymers [26, 27, 28••] or MSP depolymerisation coupled with subsequent crosslinking of shortened MSP polymers [29••]. Previously it has been argued whether force could be derived from similar actin behaviour; compare [29••] and [27]. Now for the first time both actin filament cross-linking [
Inwards, apparent membrane tension retracts the cell rear?
For the cell front, there is direct experimental data in migrating cells and a mathematical model that apparent plasma membrane tension, an inwards force, causes retraction of the cell front and can regulate cell front protrusion [34, 35••, 36••]. What of the cell rear? Mathematical modelling of keratocyte motility, although not the main part of the model, similarly proposes that an increase in membrane tension relative to a weakened underlying actin cytoskeleton pushes on the cell rear to
Comparison of mechanisms
The supply of force that is linked to driving cell rear retraction is distinct in each mechanism proposed (Figure 2) — either actin filament assembly indirectly pulls (Figure 2a), actin filament crosslinking pulls (Figure 2b), actin filament depolymerisation pulls (Figure 2c) or membrane tension pushes (Figure 2d) the cell rear forwards. Actin polymerisation as a supply of force (Figure 2a) is also separately localised within the cell front to all the others (Figure 2b–d) that operate directly
Relative importance of each type of force
It is likely that myosin II motor-based force works together either spatially, temporally, or depending on the context in which the cell moves, with these alternative types of actin-based forces within the same cell to power cell rear retraction (Table 2).
Myosin II-motor-based contractility appears to be the dominant force for cell rear retraction when larger forces are required (Table 1), such as overcoming higher adhesion to the substratum as the cell crawls over increasingly sticky [14] or
Future
The evidence is pointing towards roles for myosin II-motor-based contractility to retract the cell rear when stronger force is needed — such as to pull forwards discrete cell rear zones that are more strongly adherent to the substratum or to pull the entire cell rear over highly sticky or through tightly meshed extracellular environments. On the other hand the notion is that relatively weaker forces coupled to actin filament depolymerisation, actin filament cross-linking and cell protrusion
References and recommended reading
Papers of particular interest, published within the period of review, have been highlighted as:
• of special interest
•• of outstanding interest
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