Actin-Binding Protein Requirement for Cortical Stability and Efficient Locomotion

Abstract

Three unrelated tumor cell lines derived from human malignant melanomas lack actin-binding protein (ABP), which cross-links actin filaments in vitro and connects these filaments to plasma membrane glycoproteins. The ABP-deficient cells have impaired locomotion and display circumferential blebbing of the plasma membrane. Expression of ABP in one of the lines after transfection restored translocational motility and reduced membrane blebbing. These findings establish that ABP functions to stabilize cortical actin in vivo and is required for efficient cell locomotion.

Overexpression of EMS1/cortactin in NIH3T3 fibroblasts causes increased cell motility and invasion in vitro

“…Such cell movement is believed to be achieved through a highly regulated and dynamic network of polymerized, crosslinked actin ®laments at the leading edges of cells, termed lamellipodia (Cunningham, 1992). Cross-linking of ®lamentous actin into bundles or lattices at lamellipodia is thought to provide the protrusive force necessary for the forward extension of membranes and cell locomotion (Cunningham, 1992).…”

“…Such cell movement is believed to be achieved through a highly regulated and dynamic network of polymerized, crosslinked actin ®laments at the leading edges of cells, termed lamellipodia (Cunningham, 1992). Cross-linking of ®lamentous actin into bundles or lattices at lamellipodia is thought to provide the protrusive force necessary for the forward extension of membranes and cell locomotion (Cunningham, 1992). Actin crosslinking proteins appear to play an important role in the creation of these actin bundles/lattices, as illustrated by studies with the ABP280 cross-linking protein in human melanoma cells (Cunningham et al, 1992).…”

“…Cross-linking of ®lamentous actin into bundles or lattices at lamellipodia is thought to provide the protrusive force necessary for the forward extension of membranes and cell locomotion (Cunningham, 1992). Actin crosslinking proteins appear to play an important role in the creation of these actin bundles/lattices, as illustrated by studies with the ABP280 cross-linking protein in human melanoma cells (Cunningham et al, 1992). In melanoma cells lacking ABP280, pseudopod extension and cell locomotion is impaired; however, cell motility can be increased in these cells by expression of ABP280 (Cunningham et al, 1992).…”

“…Actin crosslinking proteins appear to play an important role in the creation of these actin bundles/lattices, as illustrated by studies with the ABP280 cross-linking protein in human melanoma cells (Cunningham et al, 1992). In melanoma cells lacking ABP280, pseudopod extension and cell locomotion is impaired; however, cell motility can be increased in these cells by expression of ABP280 (Cunningham et al, 1992). Interestingly, cortactin has recently been found to exhibit ®lamentous actin cross-linking activity and this activity is decreased when cortactin is phosphorylated by the c-src kinase in vitro (Huang et al, 1997).…”

Filamin structure, function and mechanics: are altered filamin-mediated force responses associated with human disease?

“…FLN's role in cell motility and spreading appears to be cell-type dependent. Melanoma cell lines (M2) that lack FLNA show impaired motility with cytoskeletal blebbing defects and reduced cellular elasticity that can be rescued by the transfection of FLNA (Cunningham et al 1992) increasing β-integrin Fig. 2 Structural cartoon representation of filamin A repeat domains 19-21 (Lad et al 2007) showing the non-sequential nature of the repeat domains and the N-terminal strand A of repeat 20 contributing to the domain structure of repeat 21 covering the β-integrin binding site.…”