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Results for “Tubulin Modulators”

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PubMed1984

Posttranscriptional modulation of gene expression in cultured rat hepatocytes.

The maintenance of high levels of two liver-specific mRNAs in cultured hepatocytes was achieved in a serum-free hormonally defined cell culture medium. However, this maintenance of liver-specific mRNA levels did not correlate with the level of transcription of the genes but was apparently due to increased stabilization of the tissue-specific mRNAs. The mRNA stabilization did not occur in serum-supplemented medium. In both defined and serum-supplemented medium, actin and tubulin mRNAs were also greatly increased, in both cases predominantly if not entirely due to increased mRNA stability.

Actins↗
PubMed2002

Modulated generation of neuronal cells from bone marrow by expansion and mobilization of circulating stem cells with in vivo cytokine treatment.

The aim of the present study is to determine whether the expansion and mobilization of circulating bone marrow (BM) stem cells by in vivo treatment with granulocyte-colony stimulating factor (G-CSF) and stem cell factor (SCF) increase the amount of BM-derived neuronal cells in mouse brain. The presence of BM-derived cells in the brain was traced by transplanting into lethally irradiated adults and newborns adult BM from transgenic mice that ubiquitously expressed enhanced green fluorescent protein (GFP). GFP+ and Y-chromosome+ donor-derived cells were present in several brain areas of all treated mice (cortical and subcortical areas, cerebellum, olfactory bulb). The presence of GFP+ cells expressing nuclear neural specific antigen (NeuN), neurofilament, and beta-III tubulin in cortical forebrain and olfactory bulb (OB) was higher in G-CSF-SCF treated groups (P < 0.05, analysis of variance, Fisher post hoc). We observed that overall the amount of double positive cells was higher in animals treated at birth than in adults and in OB than in forebrain areas (P < 0.05). Temporal cortical areas of cytokine-treated adult animals revealed a mean threefold increase in the number of GFP+ cells expressing the nuclear neural specific antigen (211 +/- 86 GFP+NeuN+/mm(3) in G-CSF + SCF treated mice and 66 +/- 33 GFP+NeuN+/mm(3) in control animals). GFP+ cells coexpressing neuronal markers contain only one nucleus and have a DNA index (a measure of DNA ploidy) identical to that of surrounding neurons, thus excluding donor cell fusion with endogenous cells as a relevant phenomenon under these experimental conditions. Our results indicate that G-CSF and SCF administration modulates the availability of GFP+ cells in the brain and enhances their capacity to acquire neuronal characteristics. Cytokine stimulation of autologous stem cells might be seen as a new strategy for neuronal repair in neurodegenerative diseases.

Age Factors↗
PubMedDate not supplied

3T3 cells in adipocytic conversion.

3T3 are murine cells of an established heteroploid cellular line. Some clones of this cellular line, when cultured under adequate conditions differentiate into adipocytes. During the process of differentiation, the cells undergo a change from the elongated fibroblastic shape to a round or oval form and accumulate small drops of lipids within their cytoplasma. These lipid drops fuse into one large drop which displaces the nucleus towards the periphery, giving the cell the aspect of a mature adipocyte of white adipose tissue. The cells not only change their morphology, but they also present important biochemical changes. They show a simultaneous increase in triglyceride synthesis and activity of lipogenic enzymes. There is also an increase in the response of the activity of various hormones and the de novo synthesis of the receptors to such hormones, as insulin and ACTH. During the process of differentiation important changes occur in the synthesis of various proteins, such as actin, tubulin, and other proteins which also make up the cellular cytoskeleton, forming part of the lipid transportation within the adipose cell. The adipocytic differentiation of 3T3 cells depends on adipogenic serum factors used in the supplementary culture medium. These adipogenic factors seem to play an important role in the development of adipose tissue. There are hormones, chemical agents and serum factors which modulate adipocytic differentiation. The clone must be susceptible to adipocytic differentiation, it must reach a quiescent state and find itself in adipogenic conditions for the 3T3 cells to differentiate into adipocytes. It must also carry out an DNA synthesis which is an expression of the new phenotype. The differentiation of 3T3 cells in terminal. The fact that these cells present an adipocytic conversion under physiologic conditions and with adipogenic hormones which exist in the whole animal has been demonstrated. All of these characteristics show that the 3T3 cells may be used as an adequate experimental system to analyze the events which occur during the differentiation and development of adipose tissue.

1-Methyl-3-isobutylxanthine↗
PubMed2005

Tumor necrosis factor-alpha and interleukin-18 modulate neuronal cell fate in embryonic neural progenitor culture.

Neural progenitor cells (NPCs) in developing and adult CNS are capable of giving rise to various neuronal and glial cell populations. Neurogenesis in the adult hippocampus has been found to be inhibited by a proinflammatory cytokine, interleukin-6 (IL-6), suggesting that activated microglia in the inflamed brain may control neurogenesis. Yet, little is known about the effect of microglia-derived factors on the cell fate of embryonic NPCs. In this study, we show that neurons with betaIII-tubulin immunoreactivity in the NPC culture were reduced by the condition media collected from microglia treated with endotoxin lipopolysaccharide (LPS/M-CM). Treatment with pentoxifylline (PTX), an inhibitor for tumor necrosis factor-alpha (TNF-alpha) secretion from LPS-activated microglia, blocked the reduction of betaIII-tubulin+ cells in NPC culture. Furthermore, treatment of NPCs with interleukin-18 (IL-18), a recently discovered proinflammatory cytokine, also decreased the number of betaIII-tubulin+ cells in a dose- and time-dependent manner. Surprisingly, we also observed that the remaining betaIII-tubulin+ cells in the LPS/M-CM-treated culture exhibited more branching neurites. Thus, the activated microglia-derived cytokines, TNF-alpha and IL-18, may either inhibit the neuronal differentiation or induce neuronal cell death in the NPC culture, whereas these cells may also produce factors to improve the neurite branching in the NPC culture.

Animals↗
PubMed2004

Induction of a multifactorial resistance phenotype by high paclitaxel selective pressure in a human ovarian carcinoma cell line.

Paclitaxel (PTX) is a potent anti-neoplastic agent that is highly effective in treating ovarian cancer. Nevertheless, the emergence of PTX resistance has limited the control of this disease. To gain insight into the molecular alterations accompanying drug resistance in ovarian cancer, we generated a new stable PTX-resistant ovarian carcinoma cell line. CABA I cells, which display an intrinsic PTX resistance (IC50 = 800 ng/ml), were subjected to continuous exposure to PTX. From the residual surviving cells, the highly PTX-resistant line CABA-PTX (IC50 = 256000 ng/ml) was generated and stably maintained in vitro. Analysis of beta-tubulin expression indicated that only the HM40 and Hbeta9 isotypes were expressed in both parental and resistant cells. No specific point mutations in the HM40 were detected in either cell line, but expression levels of this isotype were significantly reduced (40%) in CABA-PTX cells. Hbeta9 levels were unchanged. In those cells, PTX resistance was associated with cross-resistance to vinblastine but not to methotrexate or 5-fluorouracil. Verapamil treatment did not reverse the intrinsic drug resistance of parental cells, but partially modulated the sensitivity of CABA-PTX cells to PTX and induced total sensitivity to vinblastine. No changes in the cell surface expression of the drug efflux pumps MRP1, MRP2 and P-glycoprotein were observed. PTX influx, monitored using a fluorescent drug derivative, was significantly reduced and delayed in CABA-PTX cells as compared to the parental cells. Together, these findings suggest that more than one mechanism is involved in PTX resistance, making CABA-PTX cell line a potentially valuable in vitro tool to study multifactorial acquired drug resistance in ovarian cancer.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2006

Tubulin ligands suggest a microtubule-NADPH oxidase relationship in postischemic cardiomyocytes.

Alterations of the microtubule network, which is involved in many vital processes, occur in several pathological conditions, such as cardiac ischemia. However, the connection between the microtubule assembly state and the factors affecting myocardial reperfusion injury, especially oxidative stress, is unknown. We aimed thus to study the effects of different tubulin ligands on the changes in the microtubule network and in several markers of cell injury and oxidative activity in cardiac muscle cells submitted to a reversible substrate-free, hypoxia-reoxygenation model of ischemia-reperfusion. The microtubule network was visualized by immunocytochemistry. Cell injury was evaluated via lactate dehydrogenase release and the mitochondrial function by the MTT test. Superoxide production was detected using dihydroethidium. The activity of NADPH oxidase and mRNA subunit expression were investigated. The microtubule disassembly induced by simulated ischemia was reversed by placing cardiomyocytes under normoxic conditions. This post-"ischemic" restoration of microtubule assembly was modulated by microtubule stabilizers (taxol: paclitaxel) and by microtubule disrupting drugs (nocodazole, colchicine). In addition, nocodazole decreased superoxide anion production as well as NADPH oxidase activity and mRNA expression of the NADPH oxidase subunit p22phox. These results demonstrated that the "ischemia"-induced microtubule network alteration is reversible and suggest a possible relationship between "reperfusion"-induced reassembly of microtubules and free radical generation in post-"ischemic" cardiomyocytes.

Animals↗
PubMed1983

Fibronectin modulation of cell shape and lipogenic gene expression in 3T3-adipocytes.

The differentiation of 3T3-F442A cells is accompanied by changes in cell morphology, decreased synthesis and assembly of cytoskeletal proteins, and increased biosynthesis of lipogenic enzymes. The differentiation-dependent alterations in actin assembly can be prevented by culture of cells on fibronectin matrices. Under these conditions, morphological change is prevented and the induction of lipogenic enzymes such as glycerophosphate dehydrogenase and fatty acid synthetase is sharply reduced. In contrast, the differentiation-linked decreases in actin and tubulin biosynthesis occur normally. Hybridization of cytoplasmic and nuclear RNA to cloned cDNA probes indicates that the inhibition of lipogenic protein biosynthesis occurs because of reduced levels of specific mRNA production. The inhibitory effects of fibronectin can be reversed by keeping cells in a rounded configuration or by exposing cells to either cytochalasin D, which disrupts the actin cytoskeleton, or insulin, a key lipogenic hormone. These results demonstrate that fibronectin can regulate gene expression for lipogenic proteins and they suggest that it interferes with cytoskeletal and morphological changes necessary for new gene expression.

Actins↗
PubMed1982

Modulation of mRNA for microtubule-associated proteins during brain development.

The heterogeneity of tau microtubule-associated proteins from rat brain is developmentally determined. Newborn rat brain contains two tau polypeptides (tau 0) with somewhat different molecular weights than the five tau components associated with microtubules from 12-day-old brain (tau 12). tau 0 and tau 12 are immunologically related and crossreact with antibodies against tau 12 proteins. Enrichment of the tau mRNA was achieved by prior hybridization of unfractionated poly(A)-containing mRNA to cDNA preparations containing tubulin and actin sequences. The remaining unhybridized mRNA was further fractionated by electrophoresis on methylmercury hydroxide agarose gels. Experiments involving cell-free translation of mRNA indicated that the major differences in the composition of tau proteins from newborn and developing brain are controlled at the mRNA level. The mRNA from newborn rat brain directed the synthesis of five tau proteins, two of which are specific for newborn brain, whereas the other three forms are characteristic of the developing brain. Thus, the appearance in newborn brain of mRNA species specific for three tau 12 forms precedes the phase of the synthesis of these proteins in the cell. By contrast, mRNA from 12-day brain directed the synthesis of four tau proteins specific for the developing brain, one of which is not synthesized by mRNA from newborn brain. None of the newborn tau 0 forms were synthesized with mRNA isolated from 12-day brain.

Animals↗
PubMed1996

Specific characteristics of phosphofructokinase-microtubule interaction.

Muscle phosphofructokinase interacts with microtubule-associated protein-free microtubules resulting in a reduction of the overall activity of the enzyme [Lehotzky et al. (1993) J. Biol. Chem. 268, 10888-10894] and periodical cross-linking of the tubules [Lehotzky et al. (1994) Biochem. Biophys. Res. Commun. 204, 585-591]. Microtubule polymers of 'tail-free' tubulin obtained by removal of the carboxy-termini with limited subtilisin digestion retain the binding domains for phosphofructokinase that cross-bridges microtubule 'bodies'. Microtubule-associated proteins bound on tubulin 'tails' do not perturb the kinase binding. These data suggest that the tubulin carboxy-terminal domain is not involved in microtubule-phosphofructokinase interactions and phosphofructokinase and microtubule-associated proteins have distinct binding domains on microtubules. Of different isoforms of phosphofructokinase, occurring mainly in brain and tumor cells, the muscle isoform exhibits selective adsorption behaviour on microtubules. Phosphofructokinase M and C isoforms with different associative and allosteric properties may represent an auxiliary pathway to modulate energy production via glycolysis.

Animals↗
PubMed2000

Glutamine synthetase, hemoglobin alpha-chain, and macrophage migration inhibitory factor binding to amyloid beta-protein: their identification in rat brain by a novel affinity chromatography and in Alzheimer's disease brain by immunoprecipitation.

Proteins binding to amyloid beta-protein (Abeta) may modulate the accumulation of Abeta in Alzheimer's disease (AD) brain. We developed a monomeric Abeta column for isolation of the proteins binding to Abeta from rat brain. By amino acid sequence analysis and immunoreactivity with specific antibodies, we identified three new Abeta-binding proteins, glutamine synthetase, hemoglobin alpha-chain, and macrophage migration inhibitory factor as well as serum albumin, beta-tubulin, and glyceraldehyde-3-phosphate dehydrogenase already identified as proteins bound to amyloid beta-protein precursor. In addition, the retained fraction contained both apolipoprotein E and alpha(1)-antichymotrypsin already known as Abeta binding proteins. Furthermore, we detected the complexes of these new binding proteins with Abeta in a soluble fraction of the cerebral cortex of AD brain by immunoprecipitation. Our results suggest that these binding proteins also associate with Abeta, leading to the clearance or the accumulation of Abeta and the neuronal cell damage in human brain.

Alzheimer Disease↗
PubMed2004

Bcl-2 immunoreactive neurons are differentially distributed in subregions of the amygdala and hippocampus of the adult macaque.

The amygdala and hippocampus are key limbic structures of the temporal lobe, and are implicated in the pathology of mood disorders. Bcl-2, an intracellular protein, has recently been identified in the primate amygdala and hippocampus, and is now recognized as an intracellular target of mood stabilizing drugs. However, there are few data on the cellular phenotypes of bcl-2-expressing cells, or their distribution in specific subregions of the amygdala and hippocampus. We used a number of histochemical markers to define specific subregions of the primate amygdala and hippocampus, and examined phenotype-specific distributions of bcl-2 immunoreactive cells within each subregion. Immature-appearing bcl-2 labeled neurons, which co-contain class III beta-tubulin immunoreactivity, are found in distinct subregions in each structure. In the amygdala, bcl-2 positive neurons with an immature morphology are densely distributed in the paralaminar nucleus and intercalated cell islands, the parvicellular basal nucleus, and the ventral periamygdaloid cortex and amygdalohippocampal area. In the hippocampus, immature-appearing bcl-2-labeled cells are confined to the polymorph layer (subgranular zone), and base of the granule cell layer in the dentate gyrus. Well-differentiated neurons also express bcl-2. In the amygdala, labeled cells with mature phenotypes are concentrated in the parvicellular basal nucleus, the accessory basal nucleus, and the periamygdaloid cortex. The medial nucleus and central extended amygdala also contain many well-differentiated bcl-2 positive cells. In the hippocampus, the dentate gyrus and Ammon's horn contain many bcl-2 immunoreactive nonpyramidal cells. These are preferentially distributed in the rostral hippocampus. CA3 and CA2 contain relatively higher concentrations of bcl-2-labeled cells than CA1 and the subiculum. Bcl-2 is thus important in intrinsic circuitry of the hippocampus, and in amygdaloid subregions modulated by the hippocampus. In addition, the extended amygdala, a key amygdaloid output, is richly endowed with bcl-2 positive cells. This distribution suggests a role for bcl-2 in circuits mediating emotional learning and memory which may be targets of mood stabilizing drugs.

Amygdala↗
PubMed2000

Affinity purification and partial characterization of the zonulin/zonula occludens toxin (Zot) receptor from human brain.

The intercellular tight junctions (TJs) of endothelial cells represent the limiting structure for the permeability of the blood-brain barrier (BBB). Although the BBB has been recognized as being the interface between the bloodstream and the brain, little is known about its regulation. Zonulin and its prokaryotic analogue, zonula occludens toxin (Zot) elaborated by Vibrio cholerae, both modulate intercellular TJs by binding to a specific surface receptor with subsequent activation of an intracellular signaling pathway involving phospholipase C and protein kinase C activation and actin polymerization. Affinity column purification revealed that human brain plasma membrane preparations contain two Zot binding proteins of approximately 55 and approximately 45 kDa. Structural and kinetic studies, including saturation and competitive assays, identified the 55-kDa protein as tubulin, whereas the 45-kDa protein represents the zonulin/Zot receptor. Biochemical characterization provided evidence that this receptor is a glycoprotein containing multiple sialic acid residues. Comparison of the N-terminal sequence of the zonulin/Zot receptor with other protein sequences by BLAST analysis revealed a striking similarity with MRP-8, a 14-kDa member of the S-100 family of calcium binding proteins. The discovery and characterization of this receptor from human brain may significantly contribute to our knowledge on the pathophysiological regulation of the BBB.

Amino Acid Sequence↗
PubMed2005

New neurons in the dentate gyrus are involved in the expression of enhanced long-term memory following environmental enrichment.

Although thousands of new neurons are continuously produced in the dentate gyrus of rodents each day, the function of these newborn cells remains unclear. An increasing number of reports have provided correlational evidence that adult hippocampal neurogenesis is involved in learning and memory. Exposure of animals to an enriched environment leads to improvement of performance in several learning tasks and enhances neurogenesis specifically in the hippocampus. These data raise the question of whether new neurons participate in memory improvement induced by enrichment. To address this issue, we have examined whether the increase in the number of surviving adult-generated cells following environmental enrichment contributes to improved memory function. To this end, neurogenesis was substantially reduced throughout the environmental enrichment period using the antimitotic agent methylazoxymethanol acetate (MAM). Recognition memory performance of MAM-treated enriched rats was evaluated in a novel object recognition task and compared with that of naive and nontreated enriched rats. Injections of 5-bromo-2'-deoxyuridine were used to label dividing cells, together with double immunofluorescent labelling using glial or neuronal cell-specific markers. We found that enrichment led to improved long-term recognition memory and increased hippocampal neurogenesis, and that MAM treatment during environmental enrichment completely prevented both the increase in neurogenesis and enrichment-induced long-term memory improvement. These results establish that newborn cells in the dentate gyrus contribute to the expression of the promnesic effects of behavioural enrichment, and they provide further support for the idea that adult-generated neurons participate in modulating memory function.

Animals↗
PubMed2005

Hypoxia stimulates carcinoma invasion by stabilizing microtubules and promoting the Rab11 trafficking of the alpha6beta4 integrin.

Hypoxia plays a key role in tumor cell survival, invasion, and metastasis. Here we show that hypoxia increases tumor cell invasion by the modulation of Rab11, an important molecule for vesicular trafficking, especially membrane protein recycling and translocation of proteins from trans-Golgi network to plasma membrane. Dominant-negative Rab11 dramatically decreased hypoxia-induced invasion of MDA-MB-231 breast carcinoma cells without affecting cell apoptosis. Hypoxia-induced Rab11 trafficking is regulated by microtubule stability, as evidenced by the findings that hypoxia increases Glu tubulin and that colchicine blocks Rab11 trafficking and invasion. Inhibition of GSK-3beta activity by hypoxia seems to be central to microtubule stabilization and invasion. In fact, expression of a dominant-negative GSK-3beta was sufficient to stimulate invasion in normoxia. One target of Rab11-mediated trafficking that contributes to invasion is the integrin alpha6beta4. Hypoxia induced a significant increase in alpha6beta4 surface expression but it had no effect on the surface expression of alpha3beta1. This increase is dependent on Rab11 and stable microtubules. In summary, we identify vesicle trafficking as a novel target of hypoxic stimulation that is important for tumor invasion.

Animals↗
PubMed1992

Changes in microtubules, microtubule-associated proteins, and intermediate filaments during the differentiation of HL-60 leukemia cells.

The cytoskeleton is composed mainly of microtubules (MT), microfilaments, and intermediate filaments (IF) that form a structural network which connects cellular membranes, cytoplasmic organelles, and the nucleus. Since the cytoskeleton may be involved in modulating signal transduction and in the morphological and structural changes that occur during cellular proliferation and differentiation, cytoskeletal changes were measured by immunofluorescence microscopy and fluorescence-activated cell sorter analysis during the differentiation of HL-60 leukemia cells induced by retinoic acid (RA). Differentiated HL-60 cells exhibited increased staining intensity and altered organization of MT and IF, as visualized by immunofluorescence microscopy with anti-tubulin monoclonal antibody and anti-vimentin antibody, respectively. A new procedure was developed and used to measure the content of the cytoskeletal components of HL-60 cells during the process of maturation. HL-60 cells were fixed with formaldehyde in an MT-stabilizing buffer, permeabilized using L-lysophosphatidylcholine, stained for immunofluorescent measurement with antibodies specific for particular cytoskeletal components, and analyzed by flow cytometry. Terminally differentiated cells produced by exposure to RA contained larger amounts of MT and the IF vimentin. During the course of the maturation process, a transient increase in the amounts of the microtubule-associated proteins, (MAPs) MAP2 and tau, occurred. An RA-supersensitive clone, designated HL-60/S4, and an RA-resistant clone, designated HL-60/R3, were developed by mutagenization and selection. Use of these clones supported the concept that the observed changes in MT, MAPs, and vimentin were associated with the differentiation process rather than being due to other effects produced by the retinoid. Thus, the findings suggest that changes in MT, MAPs, and IF are important to the terminal maturation of leukemia cells.

Cell Differentiation↗
PubMed2006

Peroxynitrite-mediated tau modifications stabilize preformed filaments and destabilize microtubules through distinct mechanisms.

Alzheimer's disease (AD) is a progressive amnestic dementia typified by abnormal modifications of the microtubule (MT)-associated tau protein that promote its pathological self-assembly and displacement from the MT lattice. Previously, we showed that peroxynitrite (ONOO-) induces the oxidative 3,3'-dityrosine (3,3'-DT) cross-linking and site-selective nitration of tau monomers [Reynolds et al. (2005) Biochemistry 44, 1690-1700]. In the present study, we examined the effects of ONOO(-)-mediated modifications on two key elements of tau pathobiology: (1) the stability of preformed tau filaments and (2) the ability of monomeric tau to promote tubulin assembly. Here, we report that treatment of synthetic tau filaments with ONOO- generates heat-stable, SDS-insoluble aggregates with a significantly reduced mobility by SDS-PAGE compared to that of nontreated filaments. Ultrastructurally, these aggregates appear to be cross-linked via interfilament bridges. Using LC-MS/MS and HPLC with fluorescent detection, we demonstrate that covalent 3,3'-DT linkages are present within these higher-order aggregates. Similar to monomeric tau, filamentous tau exhibits a hierarchical pattern of nitration following ONOO- treatment with site selectivity toward the amino-terminal residues Tyr18 and Tyr29. Further, select nitration of residues Tyr18, Tyr29, Tyr197, and Tyr394, events known to stabilize the pathological Alz-50 conformation [Reynolds et al. (2005) Biochemistry 44, 13997-14009], inhibits the ability of monomeric tau to promote tubulin assembly. This effect is specific for the 3-NT modification, as mutant tau proteins pseudophosphorylated at each Tyr residue are fully competent to stabilize MTs. Collectively, our results suggest that ONOO(-)-mediated modifications stabilize tau filaments via 3,3'-DT bonding and destabilize MTs by site-selective nitration of tau monomers. Moreover, assumption of the Alz-50 conformation may be the mechanism through which tau nitration modulates MT stability.

Amino Acid Sequence↗
PubMed1995

Role of microtubule-associated proteins in the control of microtubule assembly.

In eukaryotic cells, microtubules, actin, and intermediate filaments interact to form the cytoskeletal network involved in determination of cell architecture, intracellular transport, modulation of surface receptors, mitosis, cell motility, and differentiation. Cytoskeletal organization and dynamics depend on protein self-associations and interactions with regulatory elements such as microtubule-associated proteins (MAPs). The MAP family includes large proteins like MAP-1A, MAP-1B, MAP-1C, MAP-2, and MAP-4 and smaller components like tau and MAP-2C. This review focuses on relevant aspects of MAP function, with emphasis on their roles in modulating cytoskeletal interactions. In this context, MAP expression mechanisms and posttranslational modifications are also discussed. Microtubule-associated proteins have a rather widespread distribution among cells, but certain MAPs have been identified in specific cell types. Within single neurons, MAP-2 is dendritic while tau is preferentially an axonal protein. Their expression is developmentally regulated. Even though MAPs share a capacity to interact with the COOH-terminal tubulin domain, stabilize microtubules, and link them with other cytoskeletal polymers, they exhibit structural differences. However, MAP-2, MAP-4, and tau have common repetitive microtubule-binding motifs. Microtubule-associated proteins not only control cytoskeletal integrity, but they also appear to interact with highly structural elements of cells. Molecular biological approaches permitted localization of new MAPs in cultured mammalian cells and invertebrate organisms and other microtubule-interacting proteins that exhibit transient interactions with microtubules. The structural/functional aspects of several new MAP-like proteins in centrosomes and the mitotic spindle, functionally implicated in cell cycle events, are also analyzed.

Amino Acid Sequence↗