Biology Reference
In-Depth Information
Introduction
Cell movement results from the coordinated remodelling of the cytoskeleton
and adhesion structures. The cellular machinery involved in this process is very
complex and includes not only the structural components (such as cytoskeletal
fibres, molecular motors and transmembrane adhesion receptors), but also a
plethora of adapter, regulatory and signalling proteins that control dynamics
and interactions of the core structural elements. The complexity of the cell
locomotory system is high and includes many regulatory loops, providing
proper coordination between different structural components, and enabling
this system to respond correctly to a variety of external stimuli. The major
types of external signals affecting cell motility, besides soluble chemotactic
factors and 'motogenic' ligands, are the adhesion contacts with other cells and
the extracellular matrix (ECM). In particular, integrin-mediated cell-matrix
adhesions not only physically support cell locomotion, but also generate
signals that essentially determine the character of cell motility, its direction,
velocity and persistence (Cary et al., 1999; Holly et al., 2000).
Despite the complexity of the external stimuli and the types of locomotory
responses, the general model for the cell motility regulation, as it emerges from
the studies of the last 10 years, is surprisingly uniform (Figure 5.1). The
external signals, including the signals from the adhesion receptors, are not
transduced directly to the effector mechanisms, but rather to an integrating
system based mainly on the small G-proteins of the Rho family (Kjoller and
Hall, 1999; Ridley, 2001; Schmidt and Hall, 2002) and perhaps some other
small G-proteins such as ARFs (Casanova, 2003; Turner and Brown, 2001).
Each specific stimulus is 'translated' into a specific combination of activities/
localizations of these G-proteins. The G-proteins, in turn, modulate the
activity and localization of downstream effectors, initiating cascades of events
that lead to cytoskeletal reorganization, and ultimately to alterations in
adhesion and locomotory behaviour (Bishop and Hall, 2000; Etienne-
Manneville and Hall, 2002; Ridley, 2001).
The two main cytoskeletal effectors of the small Rho GTPases are the actin
microfilaments and the microtubule system. Organization of these major
systems of cellular fibres have a surprising number of common features
(Mitchison, 1992). Both actin filaments and microtubules are polar and
demonstrate an assembly-prone, fast growing 'plus end' and a slow growing
'minus end' that favours dissasembly. Both types of fibres are associated with
molecular motors (kinesins and dyneins for microtubules, myosins for actin
filaments) that directionally move along these fibres (Cross and Carter, 2000).
Apparent structural similarity was found between the myosin and kinesin
motor domains (Vale and Milligan, 2000). The dynamics of the processes of
assembly-disassembly are in both cases rich and complex, and permit different
modes of subunit turnover at the steady state, including 'treadmilling' and
