The Structures and Functions of Microtubules - Essay Example

Using specific examples, describe the structure and function of the accessory proteins which interact with microtubules Introduction Chemically microtubules are class of fibrous proteins formed within a cell. These long, linear, and stiff polymers abound throughout the cytoplasm and are the governing structures that control the organization and function of membrane-bound organelles and other relevant components within the cell. At the molecular level, these comprise of tubulin molecules, which in turn are a heterodimer comprising of globular polypeptides, alpha and beta tubulin which are closely related and tightly linked. Many cellular functions are controlled by these microtubules which essentially are mediated through polymerisation and depolymerisation, which are controlled by nucleotide GTP. Following synthesis and during activity, there are molecular rearrangements within these microtubules are stabilized with accessory proteins, which are specific for particular tubulin (Alberts et al., 2008). In this assignment from different cellular examples, these interactions between the specific accessory proteins and the microtubule molecular structure will be examined in order to describe the structures and functions of these specific accessory proteins. Background While these filaments abound in the cytosol of the eukaryotic cells, they have been classified into three categories based on size indicated by their diameter, type of the subunit, and subunit arrangement. The smallest of them are actin filaments which have a twisted double-stranded structure of 8 to 9 nm. The largest are microtubules which are essentially hollow tubes of adjacent protofilaments of 24 nm. The intermediate filaments are 10 nm in diameter. While each type of these cytoskeletal filaments is a polymer of protein subunits, the monomeric actin subunits assemble into microfilaments, which have dimeric subunits composed of alpha and beta tubulins that polymerize into microtubules (Alberts et al., 2008). What is significant is that the intermediate filaments are assembled within the cells out of a large family of diverse proteins, which are expressed preferentially from certain tissues and often concentrated in distinct locations. Taking the example of actin filaments, which demonstrate diverse turnover rates, are closely associated with actin binding proteins which differ, and it has been postulated that they determine the differences in turnover rates. This plasticity of the internal structure of the actins is responsible for the difference in filament turnover rates in different cellular locations. This is accomplished through direct control of the filament stability and through modulation of protein binding affecting the stability of the filaments (Kueha et al., 2008). These, therefore, are mechanoskelatal proteins which convert energy released by hydrolysis of ATP or from ion gradients and generate mechanical forces. The most important feature of these proteins that while they bind, they carry their own cargo, and hence movement at a specific direction of this protein as a result of microtubular shortening would result in movement of the cargo from one location to the other within the cell. This allows an avenue of movement of the cellular proteins to the target area where further chemical reaction may take place. Thus, this is an example of accessory protein which in association with the cellular microtubules can cause sliding movement between the microtubules that are adjacent and at the same time causes movement of the cytoplasmic particles along a single microtubule to its target (Gibbon, 1988). Recent studies on accessory proteins associated with microtubules demonstrate that cytosolic dyneins are associated with retrograde transmission of intraxonal vesicles within neural tissues, and the forward motion of such vesicles is effected by another accessory protein, namely, kinesins. At the same time, within the brain neural tissues accessory proteins have been located which vary in molecular weights and binding affinities. These proteins basically have two domains, one binding to the microtubules and the other to the other cell components. In this way, these proteins are designed to link microtubules to other cell components where further reactions may take place. Moreover, the microtubule binding domain may bind to multiple unpolymerized tubulin molecules at the same time which may facilitate the nucleation stage of the polymerization of the microtubules. If analyzed from the functional point of view, these different accessory proteins in association with microtubular arrangements can confer functional diversity to different cells. In the following paragraphs, examples from different tissues will be examined how these structures and functions can be variable in different tissues with variation of accessory protein-microtubule assembly (Lodish et al., 2007). To understand these examples better, it must be taken into account that in the cytoplasm of the cell, microtubules exist in a state of dynamic instability at both ends of the chain. In this form, there are phases of growth by polymerization alternating with stochastic phases of shrinkage, which occur through a relatively faster depolymerization. This confers a general framework of polarity of the cell with morphogenesis of specific patterns yet an opening for diverse functional capabilities and motilities with contribution to cell shape and asymmetry. The association with accessory proteins plays important roles since these functional properties can be attributed to differing degrees of posttranslational acetylation and detyrosylation of the tubulin molecules, which can be brought about by the association with accessory proteins (Cordonnier et al., 2001). Martin-Verdeaux et al. (2003) indicated that compound exocytosis from human mast cells leading to expression of inflammatory mediators is a function of association between SNARE (soluble N-ethylmaleimide-sensitive fusion factor attachment protein receptor) and a series of accessory proteins. Studies have indicated that syntaxin binding Munc18 protein isoforms bind to microtubule network to facilitate this process. The mast cells express a variant of this protein, Munc-2 which interacts with target SNARE syntaxin 2 or 3. The other protein expressed by the mast cells is Munc18-3 which has affinity and demonstrable interaction with syntaxin 4. It has also been demonstrated that while 18-2 is located within the secretory granules of the mast cells, the 18-3 variant is localized in the plasma membranes. The Munc18 families of accessory proteins bind to specific sets of syntaxins which inhibit binding to cognate SNARE patterns, which in turn respond to cellular signaling mechanisms through interactions with protein kinases and phosphatases. Moreover, these accessory proteins also act as chaperones preventing degradation of the partnering syntaxins leading to generation of multiple available SNAREs (Martin-Verdeaux et al. 2003). Other studies (Gaisano et al., 2001) have indicated that functionally these two variants of Munc18 are different since they bind to different sets of syntaxins. Apart from these functions in the mast cells Munc18-2 accessory proteins have been implicated in apical membrane traffic in the epithelial cells while the 18-3 can regulate the exocytosis of GLUT4 glucose transporter and regulation of pancreatic acinar cell secretions redirecting the secretion retrograde from the apical to the basal surface (Gaisano et al., 2001). Early on Witman et al. (1976) indicated that accessory protein factors are also significant in the neural tissues. They had been demonstrated to stimulate tubulin assembly. In fact the absence of this protein designated as tau would lead to inhibition of assembly of tubulin dimers into polymers. Therefore tau accessory protein confers a facilitative structural modification to the tubulin dimers, where the initiation of the assembly is caused by association with tau proteins. The specificity of tau proteins has been indicated by other experiments which demonstrate that other positively charged macromolecules may bind with tubulins to form aggregation, however they are functionally inert as opposed to tau-associated tubulin molecules (Witman et al. 1976). Nicastro et al. (2006) demonstrated association between dynein and nexin accessory proteins. This has been described as a flexible protein that connects neighboring doublet microtubules. This structural assembly contributes to elastic resistance which converts doublet sliding into bending of the axonemes. Current research indicates that similar mechanisms may be responsible for transmission of humoral responses of the cell to different stimuli, epithelial cells with functional cilia, both peripheral and central nervous system, and in endothelial functions. The ion channel transport mechanisms that include calcium channels and sodium-potassium ATPase channels in the cardiac cells also function through microtubule assembly and its binding with different accessory proteins (Nicastro et al. 2006). Lastly, the topical review of Okamoto and Forte (2001) indicates the functional significance of such associations in vesicular trafficking machinery, present almost in all cells. This occurs through recruitment and recycling of specific membrane proteins assigned to perform specific functions. In the context of gastric parietal cells and the process of hydrochloric acid secretion, they contend that microtubules located in the apices of the parietal cells bind with H+K+-ATPase leading to remodeling of the apical membranes which begins a cascade of reactions between cytoskeleton and the vesicular trafficking machinery of these cells. Therefore, the process basically is an association between these accessory proteins and the actin based cytoskeleton with recruitment of microtubule based K+ and Cl- conductance channels. The authors state clearly that "in many cases, they have been shown to regulate protein sorting and vesicular trafficking between two membrane compartments by recruiting other effector proteins" (Okamoto and Forte 2001), thus indicating clear role of accessory proteins in this process. Conclusion It has been demonstrated that within the cell, there is continuous modification of microtubules which is conferred through a process of binding to other proteins. These are known as microtubule associated proteins or accessory proteins. The two main roles that these microtubule-accessory protein complexes perform are stabilization of the microtubular molecular structure against disassembly and more importantly mediation of their interactions with other components of the cell. Perhaps the most significant and ubiquitous protein associated with microtubules are ATPases which transduce energy. These are also known as microtubule motor proteins which induce a sliding between adjacent microtubules. Reference List Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K., and Walter, P., (2008). Garland Books. 1495-1521 Cordonnier, MN., Dauzonne, D., Louvard, D. and Coudrier, E., (2001). Actin filaments and Myosin I alpha cooperate with microtubules for the movement of lysosomes. Mol. Biol. Cell 12, 4013-4029 Gaisano, HY., Lutz, MP., Leser, J., Sheu, L., Lynch, G., Tang, L., Tamori, Y., Trimble, WS. and Salapatek, AM. (2001). Supramaximal cholecystokinin displaces Munc18c from the pancreatic acinar basal surface, redirecting apical exocytosis to the basal membrane. J. Clin. Invest. 108, 1597-1611. Gibbons, IR., (1988). Dynein ATPases as Microtubule Motors. 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