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A GFP label of the actin cytoskeleton in a melanoma cell, showing a ruffled-edge lamellipodium, from Cell Biology at IMB Salzburg.

The lamellipodium (pl. Lamellipodia) is a cytoskeletal actin projection on the mobile edge of the cell. It contains a two-dimensional actin mesh; the whole structure pulls the cell across a substrate (Alberts, et al, 2002). Within the lamellipodia are ribs of actin called microspikes, which, when they spread beyond the lamellipodium frontier, are called filopodia (Small, et all, 2002). The lamellipodium is born of actin nucleation in the plasma membrane of the cell (Alberts, et al, 2002) and is the primary area of actin incorporation or microfilament formation of the cell. Lamellipodia range from 1μm to 5μm in breadth and are approximately 0.2μm thick (Weed, et al, 2000).

Lamellipodia are found primarily in very mobile cells, in particular the keratinocytes of fish and frogs, which are involved in the quick repair of wounds, crawling at a speeds of 10-20μm/minute over epithelial surfaces. A lamellipodium separated from the main part of a cell by scratching across the cell with a pipette tip can continue to crawl freely about on its own.

Lamellipodia are a characteristic feature at the front, leading edge, of motile cells. They are believed to be the actual motor which pulls the cell forward during the process of cell migration. The tip of the lamellipodium is the site where exocytosis occurs in migrating mammalian cells as part of their clathrin-mediated endocytic cycle. This, together with actin-polymerisation there, helps extend the lamella forward and thus advance the cell's front. It thus acts as a steering device for cells in the process of chemotaxis. It is also the site from which particles or aggregates attached to the cell surface migrate in a process known as cap formation.

Structurally, the plus ends of the microfilaments (localized actin monomers in an ATP-bound form) face the "seeking" edge of the cell, while the minus ends (localized actin monomers in an ADP-bound form) face the lamella behind (Cramer, 1997). This creates treadmilling throughout the lamellipodium, which aids in the retrograde flow of particles throughout (ibid.). Arp2/3 complexes are present at microfilament-microfilament junctions in lamellipodia, and help create the actin meshwork. Arp 2/3 can only join onto previously existing microfilaments, but once bound it creates a cite for the extension of new microfilaments, which creates branching (Weed, et al, 2000). Another molecule that is often found in polymerizing actin with Arp2/3 is cortactin, which appears to link tyrosine kinase signalling to cytoskeletal reorganization in the lamellipodium and its associated structures (ibid.).

Rac and Cdc42 are two Rho-family GTPases which are normally cytosolic but can also be found in the cell membrane under certain conditions (Small, et al, 2002). When Cdc42 is activated, it can interact with Wiskott-Aldrich syndrome protein (WASp) family receptors, in particular N-WASp, which then activates Arp2/3. This stimulates actin branching and increases cell motility (Small, et al, 2002). Rac1 induces cortactin to localize to the cell membrane, where it simultaneously binds F-actin and Arp2/3. The result is a structural reorganization of the lamellipodium and ensuing cell motility (Weed, et al, 2000).

1. Alberts, Bruce, et al. Molecular Biology of the Cell. Fourth Edition. Garland Science, Taylor & Francis Group. New York, 2002: pgs 908, 931, 973-975.
2. Cramer, Louise P. Molecular Mechanism of Actin-Dependent Pretrograde Flow in Lamellipodia of Motile Cells. Frontiers in Bioscience, 2, d260-270, June 1, 1997.
3. Small, Victor J., et al. The lamellipodium: where motility begins. Trends in Cell Biology, Vol. 12 No. 3, March 2002: pgs. 112-120.
4. Weed, Scott A., et al. Cortactin Localization to Sites of Actin Assembly in Lamellipodia Requires Interactions with F-Actin and the Arp2/3 Complex. The Journal of Cell Biology, Vol.151 No.1, October 2, 2000. pgs 29-40. Available Online
5. Lamellipodia at the Department of Cell Biology at IMB Salzburg