The a-Actinin Family (actinogelin)

Page updated 27/2/03

 
a-actinin is composed of two identical anti-parallel peptides, with the actin binding domain close to the N terminus, followed by 4 spectrin-like repeats and terminating with two EF-hands (calcium binding motifs).  In calcium insensitive isoforms these EF-hands are not active.   It is thought that calcium sensitivity of actin binding arises from the proximity of the EF-hand at the tail of one molecule abutting on the actin binding head of its partner.

Figure 1.  The a-actinin dimer.  CH = Calponin homology domain. Spectrin repeats 1-4, EF = EF hands Ca²⁺ binding domains.

Other a-actinin binding proteins.
A host of proteins other than actin are known to bind a-actinin. Many of these interactions are structural, especially in muscle cells, others are involved in signalling cascades and others (such as the EPEC protein Tir) are involved in pathogenesis (Table 1).

At low concentration of a-actinin relative to actin, viscosity is increased as the filaments are linked in an isotropic gel where the filaments meet each other.  At higher concentration a-actinin bundles, draws together filaments into parallel and/or anti-parallel actin filaments.  The balance between cross-linking and bundling is determined by a number of factors, a-actinin binds to filament bundles in preference to single filaments (Gratzi et al,1992), as the local concentration of binding sites is greater, however once an isotropic gel is formed the gel becomes locked into this configuration.  If an isotrpoic gel is pulled for example with a needle, this breaks the gel and aligns the filaments in the direction of the applied force and this then tips the balance permitting bundling ().  The balance can also be tipped by the severing action of the ADF/cofilins (Maciver et al, 1991).  Severing is thought to allow the short a-actinin decorated filaments to zip together.  Once zipping the filaments are now longer able to be severed by the ADF/cofilins (as severing by this group is passive - see severing by ADF/cofilins), thus large filament aggregates are formed in vitro (Maciver et al, 1991) and possibly in vivo (Aizawa et al, 1997).

Many actin-binding proteins are regulated by polyphosphoinositides, particularly phosphatidylinositol 4,5 bis-phosphate (PIP₂).  a-actinin from chicken smooth and skeletal muscle binds PIP₂ through residues 168-184 a region within CH2 (Fukami et al, 1992; Fukami et al, 1994), the second calponin homology domain segment in the a-actinin family that strengthens the actin interaction but does not itself bind actin (Norwood et al, 2000). Whereas some (Fukami et al, 1992) find that PIP₂ increased F-actin gelating activity of a-actinin, others (Fraley et al, 2003) find that PIP₂ inhibit bundling of actin by a-actinin.  These differences probably reflect differences in the methods used.

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