The biological significance of treadmilling includes cellular movement, phagocytosis, and possibly the metastasis of cancer [1] [2].
Dynamics of the filament:
Microfilaments
Elongating the actin filament occurs when free-actin (G-actin) bound to GTP associates with the filament. Under physiological conditions, it is easier for G-actin to associate at the positive end of the filament, and harder at the negative end [3]. However, it is possible to elongate the filament at either end. Association of G-actin into F-actin is regulated by the critical concentration outlined below. Actin polymerization can further be regulated by profilin and cofilin [4]. Cofilin functions by binding to ADP-actin on the negative end of the filament, destabilizing it, and inducing depolymerization. Profilin induces ATP binding to G-actin so that it can be incorporated onto the positive end of the filament.
Microtubules
Two main theories exist on microtubule movement within the cell: dynamic instability and treadmilling [5]. Dynamic instability occurs when the microtubule assembles and disassembles at one end only. While treadmilling occurs when one end polymerizes while the other end disassembles. However, the biological significance of treadmilling in vivo is not well characterized [6]. This is due to the fact that within a living cell, many microtubules are tightly anchored at one end of the filament. Some research has suggested that the differences in critical concentration between the positive and the negative end may be a way for the cell to prevent unwanted polymerization events[6].
Critical concentration:
The critical concentration is the concentration of either G-actin (actin) or the alpha,beta- tubulin complex (microtubules) at which the end will remain in an equilibrium state with no net growth or shrinkage[3]. Critical concentration differs from the positive (CC+) and the negative end (CC-), and under normal physiological conditions, the critical concentration is lower at the positive end than the negative end. Concentrations of the respective filament subunits in between the positive critical concentration and the negative critical concentration results in a filament dynamic known as steady-state treadmilling in which one end of the filament shrinks while the other grows.
- Cell movement
- Molecular biology
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- ^ Pantaloni, Dominique; Clainche, Christophe Le; Carlier, Marie-France (2001-05-25). "Mechanism of Actin-Based Motility". Science. 292 (5521): 1502–1506. doi:10.1126/science.1059975. ISSN 0036-8075. PMID 11379633.
- ^ Cooper, Geoffrey M. (2000-01-01). "Actin, Myosin, and Cell Movement".
{{cite journal}}: Cite journal requires|journal=(help) - ^ a b dos Remedios, C. G.; Chhabra, D.; Kekic, M.; Dedova, I. V.; Tsubakihara, M.; Berry, D. A.; Nosworthy, N. J. (2003-04-01). "Actin binding proteins: regulation of cytoskeletal microfilaments". Physiological Reviews. 83 (2): 433–473. doi:10.1152/physrev.00026.2002. ISSN 0031-9333. PMID 12663865.
- ^ Remedios, C. G. Dos; Chhabra, D.; Kekic, M.; Dedova, I. V.; Tsubakihara, M.; Berry, D. A.; Nosworthy, N. J. (2003-04-01). "Actin Binding Proteins: Regulation of Cytoskeletal Microfilaments". Physiological Reviews. 83 (2): 433–473. doi:10.1152/physrev.00026.2002. ISSN 0031-9333. PMID 12663865.
- ^ Rodionov, Vladimir I.; Borisy, Gary G. (1997-01-10). "Microtubule Treadmilling in Vivo". Science. 275 (5297): 215–218. doi:10.1126/science.275.5297.215. ISSN 0036-8075. PMID 8985015.
- ^ a b "Implication of Treadmilling for the Stability and Polarity of Actin and Tubulin Polymers In Vivo". The Journal of Cell Biology. 86.