Protein microtubule-associated, biochemical

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]. 

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). 

Hoshi, M. Nishida, E. Sakai, H. Characterization of a mitogen-activated, Ca -sensitive microtubule-associated protein-2 kinase. Eur. J. Biochem., 184, 477-486 (1989)... 

Deka, J., Kuhlmann, J., and Muller, O. (1998). A domain within the tumor suppressor protein APC shows very similar biochemical properties as the microtubule-associated protein tau. Eur.J. Biochem. 253, 591—597. 

For years, it was thought that the cytosolic carboxyl termini as well as various intracellular loops of the 5-HT receptors bind to FRAPs. Efforts from our lab to identify FRAPs utilized yeast two-hybrid screens see Fig. 1 for an overview), phage display see Fig. 2 for an overview), and direct biochemical approaches (8-13). These studies led to the discovery of many 5-HT2A receptorinteracting proteins, including caveolin-1 (Cav-1), arrestin-2 (Arr-2), arrestin-3 (Arr-3), microtubule-associated protein-1A (MAP-1A), and postsynaptic density protein-95 (PSD-95) see Table 1). 

Tau pathology corresponds to the intraneuronal aggregation of microtubule-associated tau proteins into abnormal filaments. Paired hehcal filaments (PHF) are the most characteristic cytoskeletal alterations affecting numerous neurons in AD. Using a combined immunocytochemical and biochemical approach (Iqbal et al., 1989) demonshated for the first time that the microtubule-associated protein tau, a normal brain cytoskeletal protein, is a component of the PHF. The authors also indicated for the first time that posttranslational modification of tau such as phosphorylation might occur which would allow it to assemble either alone or together... 

Van DeerUn VM, Forman MS, Farmer JM, Grossman M, Joyce S, Crowe A et al (2007) Biochemical and pathological characterization of frontotemporal dementia due to a Leu266Val mutation in microtubule-associated protein tau in an African American individual. Acta Neuropathol 113 471-479... 

By biochemical and immunochemical techniques it is possible to stain three PHF components microtubule-associated protein (MAP), tau and ubiquitin. The question is whether the PHF represent intracellular amyloid deposits (Masters and Beyreuther, 1990). Both the PHF and extracellular amyloid plaques are formed from globular subunits that consist of aggregates of A4 protein. Experimentally, the amyloid protein precursor fragments are transformed to their insoluble aggregating form by meta-catalysin oxidation systems. This transformation can be prevented by radical scavengers (Dyrks et al., 1992). 

Thelen, M. and Didichenko, S.A. (1997). G-protein-coupled receptor-mediated activation of PI-3-kinase in neutrophils. Ann. New York Acad. Sci. 832, 368-382. Thompson, H.L., Shiroo, M. and SaHatvala, J. (1993). The chemotachc factor N-formylmethionyl-leucyl-phenylalanine activates microtubule-associated protein 2 (MAP) kinase and MAP kinase kinase in polymorphonuclear leucocytes. Biochem. J. 290, 483-488. 

FeUpo, V, Grau, E., Minana, M.D., and Grisolia, S. 1993. Hyperammonemia decreases protein-kinase-C-dependent phosphorylation of microtubule-associated protein 2 and increases its binding to tubulin. Fur. J. Biochem. 214 243-249. 

J. Franoon, A.M. Lmmon, A. Fellous, A. Mareck, M. Pierre and J. Nunez. Heterogeneity of microtubule-associated proteins and brain development. Eur. J. Biochem. 129 465 (1982). 

E. Nishida, T. Kiwaki and H. Sakai. Phosphorylation of microtubule associated proteins (M VPs) and pH of the medium control interaction between MAPs and actin filaments. J. Biochem. Tokyo 90 575 (1981). 

Piez KA, Reddi AH. Extracellular Matrix Biochemistry. New York Elsevier, 1984. Raxworthy MJ. Microtubules, tubulins and associated proteins. Biochem Ed 16 2-9, 1988. Ruoslahti E. Fibronectin and its receptors. Ann Rev Biochem 57 375-413, 1988. 

Daleo, G.R. Piras, M.M. Piras, R. Diglyceride kinase activity of microtubules. Characterization and comparison with the protein kinase and ATPase activities associated with vinblastine-isolated tubulin of chick embryonic muscles. Eur. J. Biochem., 68, 339-346 (1976)... 

---