Biology Reference
In-Depth Information
Integrin receptors and focal adhesions
Integrin receptors are transmembrane ab heterodimers that bind to and
recognize the extracellular matrix (ECM) and/or receptors on the surface of
other cells (Hynes, 1992). Multiple members of the integrin family have been
identified and activities of these receptors have been correlated with diverse
functions that include cell migration, differentiation and proliferation.
Integrins play a central role in cell migration by performing both an adhesive
function, linking the ECM to intracellular cytoskeletal proteins, and a signal
transduction function. The focal adhesion, which forms upon integrin
clustering, represents the adhesive complex that forms between the cell and
its surrounding ECM (Burridge et al., 1988; Critchley, 2000). The focal
adhesion serves a structural function by linking actin filaments to the ECM via
integrin receptors and associated proteins. The b integrin cytoplasmic domain
has been found to associate directly with intracellular cytoskeletal proteins,
including talin and a-actinin, and is required for the localization of integrins to
focal adhesions (Zamir and Geiger, 2001). In addition to serving a structural
function, focal adhesions also serve a signalling function by associating with
many signalling molecules including focal adhesion kinase (FAK), protein
kinase C (PKC) and Src (Clark and Brugge, 1995; Giancotti and Ruoslahti,
1999; Juliano, 2002). Many studies have demonstrated that integrin-mediated
adhesion to the ECM regulates the activity of the Rho family of GTPases
(Ren et al., 1999; Schwartz and Ginsberg, 2002). We have also demonstrated
that density of ligand can regulate signalling of the Rho family GTPases, with
a biphasic dependent regulation of the activity of Rac and Cdc42, but not
Rho, in CHOK1 cells adherent to a fibronectin-coated surface (Cox et al.,
2001).
Calpain
The calpains are intracellular calcium-dependent cysteine proteases that are
widely expressed in all mammalian cells as well as in invertebrates and fungi.
The calpain-calpastatin system plays an important role in extra-lysosomal
intracellular proteolysis. The calpain system has been implicated in basic
cellular processes including apoptosis, cell proliferation and more recently cell
migration. Studies have suggested that calpain may modulate basic cellular
processes by affecting both cytoskeletal associations and the functions of
intracellular signalling pathways (Sato and Kawashima, 2001). A role for the
calpain-calpastatin system has also been shown for a number of pathological
conditions including cardiac ischaemia, arthritis, muscular dystrophy and
Alzheimer's disease (Saido et al., 1994).
