CapZ

CapZ (capping protein, CP)

Page updated 15/5/03

An actin filament barbed end capping protein (CP) from the Z-disc of muscle (thus the name CapZ). Members of this group have been isolated from a variety of phyla, and those that have been sequenced demonstrate extensive homology in both subunits. The protein is composed of two subunits alpha and beta. Similar proteins have been isolated from species across several phyla including Drosophila, Saccharomyces, Dictyostelium (Schleicher et al, 1984), Acanthamoeba (Isenberg et al, 1980), Caenorhabditis (Waddle et al, 1993) as well as vertebrates (Kilimann & Isenberg, 1982; Casella et al, 1986). The a subunits range between 32,000 and 36,000 while the b subunits are generally smaller ranging between 28,000 and 32,00. Although both subunits are required for capping activity, thus far actin binding has only been ascribed to the b-subunit (Hug et al, 1992). Puzzlingly, although the CP demonstrate extensive homology in both subunits, it is the very end domain which seems to possess actin binding properties (Hug et al, 1992) despite the fact that at this particular part there is no detectable sequence homology between this and other species! (Hartmann et al, 1989).

Structure
Although there is no obvious homology between the a and b subunits, recent crystallographic solution (Yamashita et al, 2003) of CP from chicken muscle reveals that there is a striking resemblance of the fold of the two subunits (Figure 1).

Regulation
CPs are calcium insensitive in their binding to actin (Isenberg et al, 1980; Kilimann & Isenberg, 1982; Hartmann et al, 1989; Nachmias et al, 1996), nor or they regulated by Ca²⁺/calmodulin (Kilimann & Isenberg, 1982). Like many other actin-binding proteins, CP is regulated by phosphatidylinositol 4,5 bisphosphate (PIP₂) (Heiss & Cooper, 1991; Schafer et al, 1996; DiNubile & Huang 1997). The activity of CP are also modulates by interaction with a number of CP binding proteins (Table 1).

Protein	Function	Regulation	Reference
Actin	nucleating	PIP₂	Heiss & Cooper, 1991; Schafer et al, 1996; DiNubile & Huang 1997
Carmil	A scaffold protein		Jung et al, 2001
Hsc70	An agonist activating capping activity in Dictyostelium and Plasmodium.		Eddy et al, 1993; Tardieux et al,1998
S-100b	Localises capZ to vesicles ?		Ivanenkov et al, 1993
Twinfilin	Does not interfere with actin-binding but may localise it		Palmgren et al, 2001
V-1 (myotrophin)	Inhibits actin nucleation	?	Taoka et al, 2003
Table 1. CP binding proteins

Localization
Localization studies in non-muscle cells have not always produced a consistent picture; one member displays a nuclear distribution, while chicken CP is concentrated in cell-cell junction complexes of epithelial cells. Yeast capping proteins are found at the membrane in regions generally rich in actin (Amatruda & Cooper, 1992). In muscle cells CP is present at the Z-line independently of actin so may bind another protein partner at the Z-line (Schafer et al, 1994).

References:-

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