Microtubule Composition and Function in Eukaryotic Systems - Essay Example

? MICROTUBULE COMPOSITION AND FUNCTION IN EUKARYOTIC SYSTEMS Word count: 1013 (references and figure captions excluded) Microtubule Composition and Function in Eukaryotic Systems Eukaryotic cells are differentiated from prokaryotic cells from the presence of membrane-bound organelles, an organized nuclear region, and a cytoskeleton network that preserves the shape of the cell. The cytoskeleton and its network in particular have integral roles in maintaining the cell’s shape, facilitating in cytoplasmic streaming, as well as in the movement and arrangement of the organelles within the cell especially during cell division (Galjart, 2010). The cytoskeleton is composed of three kinds of connective fibers, the smallest of which are microfilaments, then followed by intermediate filaments, and the largest kind of fiber are the microtubules. Of these three, the microtubules have the most involvement in the cellular processes within the cell, which can be attributed to the composition as well as the mode by which the network expands or retracts within the eukaryotic cell. Microtubules are made up of ?- and ?-tubulin dimers arranged in a lattice to create a series of protofilaments (Figure 1). 13 of these filaments are laid side-by-side to form 25nm tubes. Due to the head-tail arrangement ?- and ?-tubulin dimers, the whole microtubule network is considered to be polarized, with some of the tubules growing towards the nucleus (minus end) and some shrinking away from the nucleus and elongating towards the cytoplasm (plus end), making the tubules act like polarized particles (Galjart, 2010). The plus end of the microtubules contains a guanosine-triphosphate (GTP) cap that attracts tubulin dimers connected to GTP to expand as needed (Maurer et al., 2012). The expansion or contraction of the tubes is called dynamic instability, occurring through the hydrolysis of GTP to guanosine-diphosphate (GDP), which allows the tubules to alternate between elongating (called rescue) and shrinking (called catastrophe) even if the amount of tubulin dimers available in the cell is constant (Curriea et al., 2011). Figure 2 shows the head-and-tail arrangement of the dimers, as well as to how the hydrolysis of GTP to GDP causes the microtubule fibers to undergo rescue or catastrophe. Figure 1. Arrangement of the ?- and ?-tubulin dimers within the lattice of a protofilament, with the red arrow showing the direction of growth (Maurer et al., 2012). Figure 2. The formation of a microtubule fiber consists of a dimer bound with either GTP (straight) or GDP (curved), depending on whether the plus end undergoes shrinkage (catastrophe) or elongation (rescue) (Galjart, 2010). As shown in figure 2, the plus end of an elongating microtubule fiber contains a GTP cap which attracts dimers with GTP. The straight arrangement of the GTP-containing dimers ensures that the elongating or rescuing tubules are stable enough while expanding. On the other hand, as the tubule shrinks or becomes catastrophic, the GTP-dimers undergo hydrolysis, forming GDP-dimers which curve backwards due to the dimers’ curved conformation from the loss of a water molecule. The de-polymerization of the tubule by reduction of GDP-dimers completes the shrinking process, allowing the free dimers to convert into GTP to be later used in tubule elongation processes in other parts of the cell. The polarized nature of the microtubules and the strong affinity of the GTP-caps to GTP-dimes help the microtubule-ends to actively select GTP-dimers instead of GDP-bound ones. Elongation or shrinkage of the microtubule fibers due to polymerization or addition of dimers, or de-polymerization or the reduction of dimers are able to generate forces that could push or pull the organelles within the eukaryotic cell. This alternate shrinking and elongating action by the tubules is an essential task especially during the stages of cell division when the organelles and the chromosomes are pulled towards the opposite sides of the dividing cell (Curriea et al., 2011). Proteins such as microtubule-associated proteins (MAPs) located the ends of extending microtubule fibers assist in this process by probing for the sites where the tubulin fibers could attach, allowing the microtubules to push or pull the organelles as necessary (Galjart, 2010). A subgroup of MAPs called plus-end tracking proteins (+TIPs) located at the plus end of microtubules assist in this elongation and attachment of the tubule network to the organelles via electrostatic actions and signal transductions, allowing the ends of microtubules in probing around the cytoplasm while attracting loose tubulin dimers for elongation or rescue (Maurer et al., 2012). The participation of +TIPs such as end-binding proteins (EBs) in the connection of microtubule ends to other microtubules or organelles are similar to how +TIPs connect the microtubules to other parts of the cytoskeleton network, such as the actin or microfilaments and the intermediate filaments, which in turn contribute to the integrity of the structure. +TIPs are relevant in the preservation of cellular structure due to the participation in regulating growth and shrinkage in the plus-ends of microtubules, as demonstrated in an experiment involving Drosophila melanogaster cells (Curriea et al., 2011). A kind of +TIP called Minispindles (Msps) was identified in Drosophila cells that helps localize and target the plus-ends of microtubules and assisting in polymerization by transferring the free GTP-dimers to the GTP-cap ends, and de-polymerization of the tubules by binding with kinesins that in turn hydrolyze GTP to GDP and release the dimers from the lattice. EBs rely on the mechanisms of action by the Msps, and without the interaction of Msps to EBs on the microtubule ends, the rescue or elongation of the tubules discontinue (Curriea et al., 2011). If this balance of the dynamic instability shifts towards shrinking more than elongation, the cell might not undergo mitosis properly, or its shape might collapse due to the degeneration of the connections within the cytoskeleton network. In summary, the microtubule is a major component of the cytoskeletal network that functions in keeping the cell’s shape as well as moving the organelles within the cell during mitosis. The polarized nature of the microtubule is due to the head-tail nature of its dimer components, creating a tail- or minus-end growing towards the nuclear region, and a head- or a plus-end growing towards the cytoplasm. Through the process of dynamic instability microtubules are able to elongate by attachment of GTP-dimers to a GTP-cap, and shrink through GTP hydrolysis to GDP and by detachment of GDP from the tubular structure. Proteins such as +TIPs allow for the elongation of the tubules by binding to receptors on organelles or in freely-floating dimers in the cytoplasm, assisting during mitosis when organelles have to be arranged on opposite poles. The cytoskeletal framework of the cell is maintained through the continuous processes of attracting GTP- and releasing GDP-dimers, interaction of MAPs on the tubules with either free-floating dimers or binding regions on organelles, and by signaling to other filaments within the cytoskeletal network. References Galjart, N. (2010). Plus-end-tracking proteins and their interactions at microtubule ends. Current Biology, 528-537. Maurer, S., Fourniol, F., Bohner, G., Moores, C., & Surrey, T. (2012). EB's recognize a nucleotide-dependent structural cap at growing microtubule ends. Cell, 149:371-382. Curriea, J., Stewman, S., Schimizzi, G., Slep, K., Ma, A., & Rogers, S. (2011). The microtubule lattice and plus-end association of Drosophila Mini spindles is spatially regulated to fine-tune microtubule dynamics . Molecular Biology of the Cell, 22(2): 4343-4361. Read More