Microtubules associated proteins

Lewy bodies are typical in neuronal degeneration, which is accompanied by the presence of these eosinophilic intracellular inclusions of 5-25 pm diameter in a proportion of still surviving neurons. Lewy bodies contain neurofilament, tubulin, microtubule-associated proteins 1 and 2, and gelsolin, an actin-modulating protein. 

MAP is the acronym for both, Microtubule Associated Protein and Mitogen Activated Protein. 

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

Microtubule Associated Proteins Mineralcorticoids Mineralocorticoid Receptor (MR)... 

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. 

Microtubule-associated proteins bind to microtubules in vivo and subserve a number of functions including the promotion of microtubule assembly and bundling, chemomechanical force generation, and the attachment of microtubules to transport vesicles and organelles (Olmsted, 1986). Tubulin purified from brain tissue by repeated polymerization-depolymerization contains up to 20% MAPs. The latter can be dissociated from tubulin by ion-exchange chromatography. The MAPs from brain can be resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). 

The microtubule-associated proteins MAP2 and tau both have two separate functional regions (Lewis et al., 1989). One is the microtubule-binding site, which nucleates microtubule assembly and controls the rate of elongation (by slowing the rate of assembly). The second functional domain shared by MAP2 and tau is a short C-terminal a-helical sequence that can cross-link microtubules into bundles by self-interaction. This domain has some of the properties of a leucine zipper. Likely it is responsible for the organization of microtubules into dense stable parallel arrays in axons and dendrites (Lewis et al., 1989). 

Goedert, M., Spillantini, M.G., Jakes, R., Rutherford, D., Crowther, R.A. (1989). Multiple isoforms of human microtubule-associated protein tau Sequences and localization in neurofibrillary tangles of Alzheimer s disease. Neuron 3, 519-526. 

Lewis, S.A., Ivanov, I.E., Lee, G.-H., Cowan, N.J. (1989). Organization of microtubules in dendrites and axons is determined by a short hydrophobic zipper in microtubule-associated proteins MAP2 and tau. Nature 342,498-505. 

Mandelkow, E. Mandelkow, E.-M. (1995). Microtubules and microtubule-associated proteins. Curr. Opin. Cell Biol. 7, 72-81. 

Olmsted, J.B. (1986). Microtubule-associated proteins. Ann. Rev. Cell Biol. 2,421-457. 

Vallee, R.B., Wall, J.S., Paschal, B.M., Shpetner, H.S. (1988). Microtubule-associated protein 1C from brain is a two-headed, cytosolic dynein. Nature 332, 561-563. 

Several pathological self-polymerizing systems have been biophysi-cally characterized sufficiently to permit identification of protein or peptide species that could serve as molecular targets in a structure-activity relationship. These include transthyretin (TTR) [73-76], serum amyloid A protein (SAA) [77], microtubule-associated protein tau [78-80], amylin or islet amyloid polypeptide (IAPP) [81,82], IgG light chain amyloidosis (AL) [83-85], polyglutamine diseases [9,86], a-synuclein [47,48] and the Alzheimer s (3 peptide [87-96]. A variety of A(3 peptide assay systems have been established at Parke-Davis to search for inhibitors of fibril formation that could be therapeutically useful [97]. 

FriedhoffP, Schneider A, Mandelkow EM, Mandelkow E. Rapid assembly of Alzheimer-like paired helical filaments from microtubule-associated protein tau monitored by flourescence in solution. Biochemistry 1998 37 10223-10230. 

Schweers O, Mandelkow EM, Biemat J, Mandelkow E. Oxidation of cysteine-322 in the repeat domain of microtubule-associated protein tau controls the in vitro assembly of paired helical filaments. Proc Natl Acad Sci USA 1995 92 8463-8467. 

Ferrel, J. E. Jr., Wo, M., Gerhaart, J. C., and Martin, G. S. (1991). Cell cycle tyrosine phosphorylation of p34c 2 and a microtubule-associated protein kinase homolog in Xenopus oocytes and eggs. Mol. Cell. Biol. 11 1965-1971. 

Seger, R., Ahn, N. G., Boulton, T. G., Yanopoulos, G., Panayotatos, N., Radzziejewska, E., Ericsson, L., Bratlien, R. L., Cobb, M. H., and Krebs, E. G. (1991). Microtubule-associated protein 2 kinases, ERK1 and ERK2, undergo autophosphorylation on both tyrosine and threonine residues implications for their mechanism of activation. Proc. Natl. Acad. Sci. USASS 6142-6146. 

FIGURE 8.11 Multiple signal-transduction pathways initiated by calmodulin. Calmodulin bound to Ca2+ interacts and activates many enzymes, opening up a wide range of possible cellular responses. Abbreviations MAP-2, microtubule-associated protein 2 NO, nitric oxide Tau, tubulin assembly unit. 

Gleeson JG, Lin PT, Flanagan LA, Walsh CA 1999 Doublecortin is a microtubule-associated protein and is expressed widely by migrating neurons. Neuron 23 257—271 Goldstein B, Hird SN 1996 Specification of the anteroposterior axis in Caenorhabditit elegant. Development 122 1467-1474... 

The 6-iodoacetamido derivative (6-IAF) has been used to label myosin (Ando, 1984), actin (Konno and Morales, 1985), microtubule-associated proteins (Scherson et al., 1984), and histones (Cocco et al., 1986). 

Scherson, T., Kreis, T.E., Schlessinger, J., Littauer, U., Borisy, G.G., and Geiger, B. (1984) Dynamic interactions of fluorescently labeled microtubule-associated proteins in living cells./. Cell Biol. 99, 425-434. 

The more recently identified taiep rat mutant (Table 4-2) has impaired accumulation of CNS myelin for up to 2 months followed by a period of demyelination [49], Adult taiep rats have only 10-25% of the normal amount of CNS myelin. The primary genetic lesion has not yet been identified but the mutant oligodendrocytes exhibit an abnormal accumulation of microtubules during development, suggesting that the mutation may involve a microtubule-associated protein. Biochemical and immu-nocytochemical studies indicate that excessive microtubule accumulation interferes with transport of myelin proteins and/or their mRNAs, eventually leading to a failure of myelin maintenance [49]. 

Cassimeris, L. and Spittle, C. Regulation of microtubule-associated proteins. Int. Rev. Cytol. 210 163-226,2001. 

Schoenfeld, T. A. and Obar, R. A. Diverse distribution and function of fibrous microtubule-associated proteins in the nervous system. Int. Rev. Cytol. 151 67-137,1994. 

Microtubule-associated proteins Actin-binding proteins... 

---