Microtubule associated proteins MAPs

Microtubule associated proteins (MAPs) are attached to microtubules in vivo and play a role in their nucleation, growth, shrinkage, stabilization and motion. 

The cytoskeleton also contains different accessory proteins, which, in accordance with their affinities and functions, are designated as microtubule-associated proteins (MAPs), actin-binding proteins (ABPs), intermediate-filament-associated proteins (IFAPs), and myosin-binding proteins. This chapter is focused on those parts of the cytoskeleton that are composed of microfilaments and microtubules and their associated proteins. The subject of intermediate filaments is dealt with in detail in Volume 2. 

Inactivation of the tau gene by homologous recombination results in mice that are largely normal [22], indicating that tau is a nonessential protein. This may reflect functional redundancy. Thus, mice doubly deficient in tau and the microtubule-associated protein MAP IB exhibit nervous system defects that are more severe than those in the MAP IB single knockout line. 

In resting neutrophils it is estimated that there are about 11-23 microtubules per cell, with a diameter of approximately 25 nm and a wall width of 5 nm. They are long, tubular structures made by the helical formation of tubulin molecules, which are either a- or /3-subunits, each with a relative molecular mass of 55 kDa (Fig. 4.9). Each subunit is present in equimolar amounts in a tubulin molecule, and these subunits exist as dimers of one a- and one /3-subunit. Because microtubules are polar, growth of the fibre is biased towards one end, termed the plus end. A number of microtubule-associated proteins (MAPs) affect the dynamic shape of the microtubule, and in the resting neutrophil about 35-40% of the tubulin pool is assembled, whilst the remainder can be assembled very rapidly after cell stimulation. 

There has been an intensive examination of the biochemical properties of microtubule proteins over the past 15 years, and most of the work has focused on proteins derived from neural systems. For convenience, we will deal with the molecular properties of tubulin first and then collectively consider the so-called microtubule-associated proteins (MAPs). 

Isolated microtubules always contain small amounts of larger 300-kDa microtubule-associated proteins (MAPS).330 These elongated molecules may in part lie in the grooves between the tubulin subunits and in part be extended outward to form a low-density layer around the tubule.283 309 Nerve cells that contain stable microtubules have associated stabilizing proteins.331 A family of proteins formed by differential splicing of mRNA are known as tau. The tau proteins are prominent components of the cytoskeleton of neurons. They not only interact with microtubules but also undergo reversible phosphorylation. Hyperphosphorylated tau is the primary component of the paired helical filaments found in the brains of persons with Alzheimer disease.330... 

The present volume covers Muscle and Molecular Motors . The first few chapters describe the ultrastructures of striated muscles and of various muscle filaments (myosin, actin, titin), they discuss the regulation of muscle contractile activity, and they explore the mechanism of force production and movement. The book then sets out to survey other kinds of motor systems microtubules and their interactions with both microtubule associated proteins (MAPs) and the motor proteins kinesin and dynein, the major sperm protein in nematodes, the rotary ATPases driven by or driving proton gradients, and the action of motor enzymes, polymerases, on nucleic acids. The aim throughout is to explore different molecular mechanisms of motor action in order to identify common themes. 

This pocket in /(-tubulin, where microtubule-stabilizing drugs from different organisms can bind, also binds the assembly-promoting repeat motifs of tau protein (and other microtubule-associated proteins [MAPs]). It lies above the /(-sheet of the second domain and next to the core helix (Figs. 3 and 4), so that anything that fills it is in contact with the core helix and with the M-loop. When assembled in microtubules, the pocket is located on the inside face. In a-tubulin, the corresponding... 

MT interact with a large number of other proteins that modulate the MT dynamic stability or that act as active motor proteins. Microtubule-associated proteins (MAPs) stabilize MT by binding to polymers and promoting interactions with other cellular components [7], Other proteins, like those of the stathmin family, destabilize MT [8] either by preventing assembly or by promoting disassembly of MT. 

Abbreviations 3,5,3, 5 -tetraiodothyronine or thyroxine, T4 3,5,3-triiodothyronine, T, 3,3, 5 -triio-dothyronine, reverse T, or r-T3 3,5,3, 5 -tetraiodothyroacetic acid, TETRAC 3,5,3 -triiodothyroacetic acid, TRIAC 3,5-diiodotyrosine, DIT 3-monoiodotyrosine, MIT thyrotropic hormone, TSH thyreo-liberin, TRH growth hormone, GH microtubule associated proteins, MAPs TAU protein, one of the brain MAPs. 

The basic biology and pharmacology of Epo B (as the most potent and most widely studied natural epothilone) have been summarized in several previous review articles.As indicated in Section 1.1, the biological effects of the compound are based on its ability to bind to microtubules and alter the intrinsic stabihty and dynamic properties of these supramolecular structures. In cell-free in vitro systems, this is demonstrated by the prevention of Ca - or cold-induced depolymerization of preformed microtubule polymers as well as by the promotion of tubuhn polymerization (to form microtubule-like polymers) in the absence of either microtubule-associated proteins (MAPs) and/or guanosine triphosphate (GTP), at temperatures significantly below 37 °C, and in the presence of The latter... 

Tau protein is a neuronal microtubule associated protein (MAP) that localizes primarily in the axon (Leger et al., 1994). It is one of the major and most-studied MAPs in the central nervous system (Alonso et al 2001). Tau has been recognized to play major roles in promoting microtubule assembly, stabilizing microtubules and maintaining the normal morphology of the neurons. Tau has been the focus of intense research for more than a decade after it was discovered to be a key component of neurofibrillary tangles in Alzheimer s disease (AD). 

The length of the microtubule cylinder may measure upto 10,000 A, but the diameter is usually 180-250 A. The polymerisation of tubulins to microtubules takes place at 37°C in presence of Mg ions, endogenous cofactors such as GTP and microtubule-associated proteins (MAPs). The depolymerisation of microtubules occurs at temperatures lower than 37°C and in presence of Ca ions. The assembly and disassembly of microtubules proceeds in a nucleated fashion and is associated with a number of cellular functions. The formation of microtubules are required to control various cell activities such as cytoplasmic movement, cell division, cell shape and substrate and vesicle transport etc. Thus, interruption of the microtubulin assembly by a chemotherapeutic agent would result in several cellular dysfunctions leading to death of the parasites. Several drugs are known to bind with tubulin and block its polymerisation into microtubules. This results in gradual disappearance of microtubules from the cells. Consequently cytoplasmic movement and transport of nutrients are disturbed. These abnormal conditions cause death of the cell [59,60]. 

A large number of proteins influence the assembly and stability of microtubules and their association with other cell structures (Table 20-1). These proteins are collectively called microtubule-associated proteins (MAPs) because most co purify with microtubules isolated from cells. The results of Immunofluorescence localization studies also have shown a parallel distribution of MAPs and microtubules in cells— strong evidence for their interaction In vivo. 

Microtubule-associated proteins (MAPs) organize microtubules and affect their stability. Some MAPs prevent... 

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