3. Lateral movement and Stasis

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Steps in Formation

Overview

1. Initiation
2. Extension
3. Lateral movement and Stasis
4. Adherence
5. Pulling
6. Retraction and Collapse

Functional Modules

Filopodia

Step 3. Lateral Movement and Stasis

Filopodia are motile structures, being able to extend, retract and move laterally as they sense their environment. Lateral movement is particularly important to allow the structure to sense stimuli prior to its adhesion with another cell or substrate. Lateral movement may be a consequence of filopodial protrusions being tilted with respect to the retrograde flow of actin [1, 2]. This movement is inhibited once filopodia adhere to cells or substrates [3], however it is important to note that newly emerged filopodia seldom adhere to the substratum at their tips and are instead more likely to adhere at their bases [4].

Lateral movement and merging of filopodia may also stimulate further elongation of filopodia, suggesting that this may be an alternative method for promoting filopodial maturation and growth cone advancement on less adherent substrates [3].

Figure: Lateral movement of filopodia. The direction of cell movement in a migrating cell is primarily controlled by actin filament assembly at the leading edge. In the diagram above, increased actin polymerization at the side of the filopodium (yellow arrow) pushes the membrane forward and to the left (panel #1). The forces produced by actin polymerization against the actin bundles of a filopodium can lead to lateral movement (panels #2 & 3). Under the microscope, filopodia appear to cross-over one another as distinct units when they are separated within the three-dimensional framework of the cell (panels #4-6). When a laterally moving filopodium encounters another filopodium within the same three-dimensional space, the two filopodium can fuse to become one; this frequently increases the width and length of the resulting filopodium (panels #7 & 8).

Typically filopodia are quite dynamic and are constantly growing or retracting. Thus, periods of stasis are often short-lived and even adhesion of the filopodial tip to a substrate will not last long before the cell pulls on the site and recruits additional components or retracts, leaving behind a thin tube of membrane. There are several events that may promote stasis in retracting filopodia.

Mechanics of Stasis

1) Ligand binding to filopodial receptors and subsequent adhesion of the ligand/receptor complex to actin bundles
After a ligand binds to a receptor on the filopodium, lateral connections between the receptor and the actin bundle(s) prevent retrograde actin movement relative to the ligand.This inhibition converts the previous retrograde movement of the retracting filaments into tension on the bundles. This tension might influence polymerization and stability of actin filaments and/or myosin activity.

2) Ligand binding to filopodial receptors followed by uncapping of filament barbed ends
Retracting filopodia become static when receptor binding leads to filament uncapping and rapid polymerization at the barbed end. The retraction force is converted to retrograde flux and the filament length remains constant.

3) Capping of unstable actin filaments [5]
If retraction occurs by barbed end disassembly, capping of unstable filaments by an activated receptor will block retraction and induce stasis.

References

Small JV. Lamellipodia architecture: actin filament turnover and the lateral flow of actin filaments during motility. Semin. Cell Biol. 1994; 5(3):157-63. [PMID: 7919229]
Oldenbourg R., Katoh K. & Danuser G. Mechanism of lateral movement of filopodia and radial actin bundles across neuronal growth cones. Biophys. J. 2000; 78(3):1176-82. [PMID: 10692307]
Steketee MB. & Tosney KW. Three functionally distinct adhesions in filopodia: shaft adhesions control lamellar extension. J. Neurosci. 2002; 22(18):8071-83. [PMID: 12223561]
Steketee M., Balazovich K. & Tosney KW. Filopodial initiation and a novel filament-organizing center, the focal ring. Mol. Biol. Cell 2001; 12(8):2378-95. [PMID: 11514623]
Mitchison T. & Kirschner M. Cytoskeletal dynamics and nerve growth. Neuron 1988; 1(9):761-72. [PMID: 3078414]