Disease relevance of Mtap2

• These cerebellar xenografts displayed histologic features and immunohistochemical profiles (microtubule-associated protein 2, glial fibrillary acidic protein, and vimentin) similar to human medulloblastomas [1].
• To investigate the protective effects of lithium against HIV-gp120-mediated toxicity in vivo, mice were exposed to lithium and gp120 and levels of the neuronal markers, microtubule-associated protein-2 and NeuN, and the astrocyte marker, glial fibrillary acidic protein, were determined [2].
• Levels of neuron-specific nuclear protein, microtubule-associated protein 2, and neurofilament antigens were reduced significantly in the brain regions injected with human MDM infected with HIV-1DJV or VSV/HIV-1 [3].
• Transient loss of microtubule-associated protein 2 immunoreactivity after moderate brain injury in mice [4].
• When cultured mouse neuroblastoma N2A cells were examined by immunofluorescence microscopy the antiserum to MAP-1 brightly stained filamentous structures resembling microtubules, whereas relatively weak and diffuse staining of the cytoplasm was observed with the antiserum to MAP-2 [5].

Psychiatry related information on Mtap2

• The microtubule-associated protein MAP2 is a prominent large-sized component of purified brain microtubules that, like the 36- to 38-kilodalton tau proteins, bears antigenic determinants found in association with the neurofibrillary tangles of Alzheimer's disease [6].

High impact information on Mtap2

• A candidate for this link is MAP2 kinase, which is rapidly activated by tyrosine/threonine phosphorylation following mitogenic stimulation [7].
• Organization of microtubules in dendrites and axons is determined by a short hydrophobic zipper in microtubule-associated proteins MAP2 and tau [8].
• Microtubule-associated protein MAP2 shares a microtubule binding motif with tau protein [6].
• These data imply that the carboxyl-terminal domain containing the 18-amino acid repeats constitutes the microtubule binding site in MAP2 [6].
• To understand their differential localization, we performed transfection studies on primary cultured neurons using tagged tau, MAP2, MAP2C, and their chimeric/deletion mutants [9].

Chemical compound and disease context of Mtap2

• We were able to achieve statistically significant differences in toxicity between intermediately toxic concentrations of glutamate (30, 50, and 100 microM) with the MAP2 assay, while we were not able to discriminate among these concentrations with the LDH assay [10].

Biological context of Mtap2

• However, strong up-regulation of Mtap2 transcript in these mice was found by quantitative RT-PCR (qRT-PCR), indicating that Mtap2 is normally suppressed by BMP [11].
• Together, these data suggest that JNK phosphorylation of MAP2 plays an important role in defining dendritic architecture in the brain [12].
• These results suggest that MAP2 and MAP1B have overlapping functions in neuronal migration and neurite outgrowth by organizing microtubules in developing neurons both for axonal and dendritic morphogenesis but more dominantly for dendritic morphogenesis [13].
• MAP2 is required for dendrite elongation, PKA anchoring in dendrites, and proper PKA signal transduction [14].
• Increased microtubule stability and alpha tubulin acetylation in cells transfected with microtubule-associated proteins MAP1B, MAP2 or tau [15].

Anatomical context of Mtap2

• After retinoic acid (RA) treatment and in the absence of doxycycline, neuronal progenitor cells in the p19 clone were found to extend their processes towards the neighboring colony to form network-like connections, as revealed by neuron-specific microtubule-associated protein 2 staining and laser scanning confocal microscopy [16].
• In spite of the morphological constancy of glial substrata at plating, MAP2-positive cells in cocultures showed differences in the aggregation of somata and in the length, caliber, and branching of neurites [17].
• Nearly 10% of MAB1281(+) cells colocalized with GFAP, a marker of astrocytes, and MAP-2, a marker of neurons [18].
• Transcripts encoding GAP-43, MAP2 and isoforms beta APP695, beta APP714 and beta APP751 were present in normal substantia nigra and progressively reduced in weaver substantia nigra; such a reduction was correlated with dopamine neuron loss [19].
• MSCs from Wt mice continued expressing apoE up to 6 months after implantation and were associated with enhanced novel object recognition and increased microtubule-associated protein 2 (MAP2) immunoreactivity in the dentate gyrus [20].

Associations of Mtap2 with chemical compounds

• These results clearly indicate that 41- and 43-kDa proteins, the increased tyrosine phosphorylation of which is rapidly and commonly induced by mitogen stimulation of fibroblasts, are family members of ERKs/MAP2 kinases and that phosphorylation both on tyrosine and threonine residues is necessary for their activation [21].
• The cells differentiated into microtubule-associated protein-2 (MAP2)-positive neuronal cells and glial fibrillary acidic protein (GFAP)-positive glial cells. gamma-Aminobutyric acid-positive cells and tyrosine hydroxylase-positive cells were also observed in the spheres [22].
• Some cells in the later stratum displayed MAP2-, gamma-aminobutyric acid (GABA)- and calretinin immunoreactivities [23].
• The disruption of MAP2 staining was associated with a significant reduction in overall dendritic length and projection depth of biocytin labeled CA1 neurones [24].
• The neurons are present in several mammals, including primates and birds, and have a profuse dendritic arbor that expresses both the neuron-specific marker, microtubule-associated protein-2, and the neurokinin-1 receptor, a target of the neuropeptide, substance P [25].

Physical interactions of Mtap2

• MAP2 also has a binding domain for the regulatory subunit II of cAMP-dependent protein kinase (PKA) [14].

Co-localisations of Mtap2

• In the E18 cortex, L1 colocalized with microtubule-associated protein 2, a marker of dendrites and somata [26].

Regulatory relationships of Mtap2

• Moreover, we confirm that MAP2-dependent process elongation is enhanced after activation of JNK [12].
• The prevention of MAP1A, MAP1B, and MAP2 proteolysis by antioxidants highlights the early reactive oxygen species generation in the perturbation of the microtubule network induced by soluble Abeta [27].
• Enforced expression of Evi1 in P19 cells induced neuron-specific microtubule-associated protein-2 microtubule-associated protein-2 and TrkA expression in the absence of RA under monolayer culture [28].

Other interactions of Mtap2

• Regional distribution of amyloid beta-protein precursor, growth-associated phosphoprotein-43 and microtubule-associated protein 2 messenger RNAs in the nigrostriatal system of normal and Weaver mutant mice and effects of ventral mesencephalic grafts [19].
• Simultaneously, most of the cells expressed nestin but not microtubule-associated protein 2 (MAP2), and remained undifferentiated [29].
• Moreover, based on MAP2 staining of tissue sections from E12.5 embryos the topography of newly generated neurons also appeared to be undisturbed in the telencephalon of PS1-/- embryos [30].
• High hybridization signals were obtained for GAP-43, MAP2, beta APP695, beta APP714 and beta APP751 RNA transcripts in the grafted tissue; the beta APP770 species--normally seen in striatum and not substantia nigra--was not expressed in the grafts, but it was present in the recipient striatum [19].
• In addition, although Tg2576 mice showed a progressive decrease in synaptophysin and MAP2 in the CA3 area of hippocampus compared with control B6SJL at 9, 12, and 16 months, the APPQ-/- mice had significantly less of a decrease in these markers at 12 and 16 months [31].

Analytical, diagnostic and therapeutic context of Mtap2

• Fixed cocultures (Ll, Lm, Mm, Ml) were stained with an anti-MAP2 antibody to verify neuronal aggregation and neuritic morphology [17].
• Double in situ hybridization confirmed selective CTGF mRNA expression on a subpopulation (approximately 35%) of microtubule-associated protein 2 mRNA-positive neurons in the cortical layer VII and the dorsal endopiriform nucleus [32].
• To investigate whether differential turnover of MAPs contributes to localization of other major MAPs in general, we microinjected biotinylated tau, MAP2C, or MAP2 into mature spinal cord neurons in culture (approximately 3 wk) and then analyzed their fates by antibiotin immunocytochemistry [33].
• Immunoblotting indicated once again that MAP 1A, MAP 1B, and MAP 2 were included among the MAPs [34].
• Double immunolabeling confirmed that BMC migrating to the brain expressed hematopoietic but not neural markers, such as nestin, microtubule-associated protein-2 and glial fibrillary acidic protein, even 4 and 18 weeks after bone marrow transplantation [35].

References