Cellular+Motility+and+Elements+of+the+cytoskeleton

Cellular motility is largely a function of three main cytoskeleton elements: Actin, microtubules, and intermediate filaments. Actin is a double-stranded polymer consisting of actin monomers which tend to be most concentrated in the cortex of the cell. Microtubules are long, hollow cylinders made of tubulin monomers which tend to be cylindrical in shape. They are highly rigid and typically have one end attached to a Centro some in the cell. Intermediate filaments are rope-like fibers composed of a protein family known as the intermediate protein family. They typically comprise the nuclear lamina of the cell.

As previously stated, the purpose of these elements are to create motility, or cellular motion. When cells move, protrusive structures are extended to a leading edge of the cell that contains newly-synthesized actin. Additionally, the cytoskeleton rearranges itself to accommodate the change in cellular shape. Actual motion is caused by a process known as tread milling,. Treadmilling involves filaments that can either be in the T form (Active form that contains ATP/GTP) or the D form (Inactive form that contains ADP/GDP). In tread milling, T filaments are recruited at the fast-moving end of the cell (The + end) while D filaments are shed from the slow moving end of the cell. The result is a net movement toward the + end. Figure 1 illustrates this process:

Parkinson’s disease is associated with the malfunctioning of microtubules. The Parkinson’s disease toxins depolymerize the microtubules which causes the disruption of vesicular transport (Feng et al., 2006). These trapped vesicles then linger as they produce high amounts of dopamine through leakage. The dopamine links cause a high amount of oxidation in the neurons, resulting is systematic degradation and subsequently the neurological effects associated with Parkinson’s. Rodionov and Borisy are two individuals responsible for elucidating the mechanism by which tread milling occurs. In fis melanophores, they observed that microtubules detached from their nucleation site and depolymerized at the end of the cell, while accumulating at the front of the cell (Rodionov et al., 1997).

The research article “Arp2/3 complex is essential for actin network treadmilling as well as for targeting of capping protein and cofilin” (Koestler et al., 2013) describes the importance of Arp2/3 in its ability to organize actin fibers at the + end of the cell. An important fact that was revealed is that arp2/3 has no effect on the turnover of actin located at the cell periphery, indicating that another complex must be responsible for this. The research article “3 Methods to Measure Actin Treadmilling Rate in Dendritic Spines” (Koskinen et al., 2012) describes three procedures for measuring the tread milling rate of actin. The first method utilized primary cultures along with subsequent transient transfection. The second method is detection through photo bleaching and then measuring the rate through fluorescence recovery. The final method involves measurement through a photo activation assay. The research article “Treadmilling and length distributions of active polar filaments” (Erlenkämper et al., 2013) shows that a single actin filament can self-organize into a tread milling state for a wide ranger of monomer concentrations. This article also reveals that tread milling can be performed in vitro as long as the correct depolymerization promoting factors are present.

References Feng, J. (2006). Microtubule: a common target for parkin and Parkinson’s disease toxins. The Neuroscientist, 12(6), 469-476.

Koskinen, M., Bertling, E., & Hotulainen, P. (2012). 3 Methods to Measure Actin Treadmilling Rate in Dendritic Spines. Methods in enzymology, 505, 47.

Koestler, S. A., Steffen, A., Nemethova, M., Winterhoff, M., Luo, N., Holleboom, J. M., ... & Rottner, K. (2013). Arp2/3 complex is essential for actin network treadmilling as well as for targeting of capping protein and cofilin. Molecular biology of the cell, 24(18), 2861-2875.

Erlenkämper, C., & Kruse, K. (2013). Treadmilling and length distributions of active polar filaments. The Journal of chemical physics, 139(16), 164907-164907.