Biology Reference
In-Depth Information
Figure 3.1 A model for actin nucleation and elongation, and some important questions.
The popular dendritic nucleation model implies that upon reception of a stimulus (A) that
leads to cell polarity through a signalling cascade that includes GTPases and lipid kinases
(B), specific proteins can be relieved from an autoinhibitory conformation, recruit and
activate the Arp2/3 complex (C) in close proximity to the membrane (D). During
elongation, ATP-G actin is added at the growing barbed end of nascent actin filaments (E).
These major steps are under intense investigation to solve the following questions. What is
the range of stimuli that can lead to cell polarity and engagement of the actin dynamics
machinery? (A?). Which GTPases, trimeric Gs and small GTPases of the Rho/Rac/Cdc42
family are involved and by which GEF are they activated? (B?). Beside the best
characterized Arp2/3 activators of the WASp family, what other proteins can act in this
pathway? (C?). How is the seed F-actin positioned close to the plasma membrane? (D?). Is
the 'fuel' for elongation, ATP-G actin, preconcentrated at the growing end and is it bound
by WH2 domain proteins and/or in the form of profilin-actin complex? (E?). Other factors,
including capping proteins and cofilin, are crucial for motility but are not discussed here
so-called TEDS rule (Bement and Mooseker, 1995) by having a negatively
charged amino acid residue (Asp (D), Glu (E) or phosphorylatable Ser (S) or
Thr (T)) at a position of the head domain known as the cardiomyopathy loop,
and crucial for activity. In class I myosins of lower eukaryotes, this site is
phosphorylated by kinases of the PAK/Ste20 family, which are regulated by
small GTPases of the Rho/Rac/Cdc42 family (reviewed in de la Roche and
Cote (2001)). The neck or middle domain acts as a lever (Geeves, 2002)
stiffened by the binding of light chains belonging to the superfamily of
calmodulin-like EF hand proteins (Wolenski, 1995). Finally, via binding to
Search WWH ::




Custom Search