Aldolase

Aldolase

Page updated 14/5/03

A glycolytic enzyme which like a few others (phosphofructokinase, enolase, hexokinase) (Grazi et al, 1989) binds actin filaments probably in order to increase efficiency by locally concentrating enzyme and substrate. Aldolase was one of the first proteins discovered to be an actin-binding protein (Pette & Brandau, 1962). When assayed by photobleach recovery (Pagliaro & Taylor, 1988), a proportion of cellular aldolase is seen to be immobilised (presumably because aldolase exists as a trimer which explains its weak in vitro bundling activity (Wang et al, 1996; Maciver et al, 1991).

The sequence 32-ADESTGSIAKRLQSIGTENTE-52 of aldolase has been identified as the actin-binding motif (O'Reilly & Clarke, 1993). In addition, arginine 42 (highlighted in blue) when mutated to alanine show reduced actin-binding (Wang et al, 1996).

The binding of aldolase to actin is reduced in the presence of the enzymes substrate, fructose 1,6-bisphosphate (Pagliaro & Taylor, 1992). The binding of aldolase to actin may function as a feed back system, as the glucose transporter GLUT4, is connected to actin via aldolase (Kao et al, 1999), a connection presumably broken by the association of the enzyme with its substrate. The GLUT4 glucose transporter is translocated to the plasma-membrane (from a vesicular pool), when the cell is stimulated by insulin and this process seems depended on the actin cytoskeleton and its interaction with aldolase as those agent that prevent the aldolase:actin interaction also prevent the GLUT4 translocation. Aldolase also binds to the vacuolar H⁺-ATPase (Lu et al, 2001) presumably to regulate it.

Aldolase has recently been reported to form a link between a cell surface adhesin of apicomplexans (Toxoplasma, Plasmodium)and the underlying actin cytoskeleton (Jewett & Silbey, 2003).

References:-

Baque, S., Guinovart, J. J. & Ferrer, J. C. (1997) Glycogenin, the primer of glycogen synthesis, binds to actin. FEBS letter. 417, 355-359.

Bauer, A. C., Pette, D., Roisen, F. & Amberson, W. R. (1964) Fed.Proc. 23, 310.

Grazi, E. & Guidoboni, M. (1989) Opposite effects of alfa-actinin and of fructose 1,6 -bisphosphate aldolase on the microfilament network. The role of orthophosphate revisited. Biochem. Int. 19, 1345-1353.

Jewett, T. J. & Sibley, L. D. (2003) Aldolase forms a bridge between cell surface adhesins and the actin cytoskeleton in apicomplexan parasites., Mol.Cell. 11, 885-894.

Kao, A. W., Noda, Y., Johnson, J. H., Pessin, J. E. & Saltiel, A. R. (1999) Aldolase mediates the association of F-actin with the insulin-responsive glucose transporter GLUT4. J.Biol.Chem. 274, 17742-17747.

Kusakabe, T., K. Motoki, et al. (1997). Mode of interactions of human aldolase isozymes with cytoskeletons. Archiv.Biochem.Biophys. 344(1), 184-193.

Lu, M., Holliday, S., Zhang, L., Dunn jr, W. A. & Gluck, S. L. (2001) Interaction between aldolase and vacuolar H+-ATPase. Evidence for direct coupling of glycolysis to the ATP-hydrolyzing proton pump. J.Biol.Chem. 276, 30407-30413.

Maciver, S. K., Wachsstock, D. H., Schwarz, S. H. & Pollard, T. D. (1991) The actin filament severing protein actophorin promotes the formation of rigid bundles of actin filaments crosslinked with alpha actinin., J. Cell Biol. 115, 1621-1628.

O'Reilly, G. & Clarke, F. (1993) Identification of an actin binding region in aldolase. FEBS letters. 1, 69-72.

Pagliaro, L. & Taylor, D. L. (1988) Aldolase exists in both the fluid and solid phases of cytoplasm. J.Cell Biol. 107, 981-991.

Pagliaro, L. & Taylor, D. L. (1992) J.Cell Biol. 118, 859-863.

Pette, D. & Brandau, H. (1962) Biochem.Biophys.Res.Comm. 9, 367-370.

Vertessy, B. G., Orosz, F., Kovacs, J. & Ovadi, J. (1997) Alternative binding of two sequential glycolytic enzymes to microtubules. J.Biol.Chem. 272, 25542-25546.

Wang, J., Morris, A. J., Tolan, D. R. & Pagliaro, L. (1996) The molecular nature of the F-actin binding activity of aldolase revealed with site-directed mutants. J.Biol.Chem. 271, 6861-6865.

Wang, J., Tolan, D. R. & Pagliaro, L. (1997) Metabolic compartmentation in living cells: structural association of aldolase. Exp.Cell Res. 237, 445-451