FAK-Dependent Cell Motility and Cell Elongation

Abstract

Fibroblastic cells show specific substrate selectivity for typical cell-substrate adhesion. However, focal adhesion kinase (FAK) contributes to controlling the regulation of orientation and polarity. When fibroblasts attach to micropatterns, tyrosine-phosphorylated proteins and FAK are both detected along the inner border between the adhesive micropatterns and the nonadhesive glass surface. FAK likely plays important roles in regulation of cell adhesion to the substrate, as FAK is a tyrosine-phosphorylated protein that acts as a signal transduction molecule at sites of cell-substrate attachment, called focal adhesions. FAK has been suggested to play a role in the attachment of cells at adhesive micropatterns by affecting cell polarity. Therefore, the localization of FAK might play a key role in recognition of the border of the cell with the adhesive micropattern, thus regulating cell polarity and the cell axis. This review discusses the regulation and molecular mechanism of cell proliferation and cell elongation by FAK and its associated signal transduction proteins.

Keywords: FAK; c-Src; cell elongation; cell motility; focal adhesion.

Figure 1

Schematic illustration of apical plaque and focal adhesion. Extracellular matrix, integrin, and cytoskeletal proteins, such as talin, paxillin, and vinculin, are localized in both the apical plaque and the focal adhesions. FAK–Src complex is also localized in both the apical plaque and the focal adhesions at the basal portion of the cell, which indicates that the complex acts as signal transduction machinery. Localization of FAK in apical plaque is very few or not detected [60].

Figure 2

Time-lapse imaging of living fibroblasts adhering to adhesive micropattern (width: 10 µm). The cells were aligned along the longitudinal axis of adhesive micropatterns within 2 h. Adherent cells were not observed on the nonadhesive region of the glass surface. The time intervals are indicated at the top left in minutes. Phase contrast microscopy. See also a supplemental movie for live imaging and Materials and Methods. Scale: 20 µm.

Figure 3

Schematic illustration of a cell adherent on the border of the adhesive and nonadhesive micropatterns. Focal adhesions at the bottom of the cells and the apical plaque are shown. Focal adhesion kinase (FAK) is highly accumulated at the border between adhesive and nonadhesive micropatterns, and the FAK seems to be tyrosine phosphorylated. The asterisk indicates tyrosine phosphorylated active FAK.