Disease relevance of MAP2

• Finally, MAP1b mRNA was expressed in all 5 glioma cell lines, whereas MAP2 mRNAs were detected in only 3 of the cell lines [1].
• Mature ganglion cells were also immunoreactive for proteins associated with the neuronal cytoskeleton (including microtubule-associated proteins, MAP2 and tau, and higher molecular weight phosphorylated and non-phosphorylated neurofilament subunits), neuron-specific enolase, and synaptophysin [2].
• Six of these cell lines contained mRNA for the microtubule-associated protein (MAP) known as MAP1b, whereas MAP2 mRNAs were detected only in 1 of the PNET cell lines [1].
• RT-PCR, Western blot analysis, and in situ hybridization confirmed the expression of MAP2A-C (including the novel MAP2+ 13 transcript) in both oligodendrogliomas and astrocytomas [3].
• These features render MAP2 immunoreactivity a helpful diagnostic tool for the distinction of oligodendrogliomas and other neuroepithelial neoplasms [3].

Psychiatry related information on MAP2

• Microtubule-associated protein 2 (MAP2) and tau, which is involved in Alzheimer's disease, are major cytoskeletal proteins in neurons [4].
• Reduced spinophilin but not microtubule-associated protein 2 expression in the hippocampal formation in schizophrenia and mood disorders: molecular evidence for a pathology of dendritic spines [5].
• Expression of MAP2 does not seem to indicate difficulty of task or duration of training time, whereas increases in synaptophysin expression, which appear diffusely across the cortex, seem to be correlated with the first 5 days of motor skill learning [6].
• (3) Learned helplessness rats showed increased expression of MAP-2 eight days after the attainment of learned helplessness [7].
• Here we studied the expression of the neuronal cytoskeletal microtubule-associated protein 2 (MAP2) following long-term alcohol consumption and subsequent alcohol withdrawal [8].

High impact information on MAP2

• However, MAP-2, MAP-4, and tau have common repetitive microtubule-binding motifs [9].
• We show here that the mRNA and protein for the microtubule component MAP2 is also induced by retinoic acid [10].
• Inhibition of MAP2 expression affects both morphological and cell division phenotypes of neuronal differentiation [10].
• The results suggest that MAP2 expression may be necessary for both neurite extension and cessation of cell division [10].
• The resultant P/Talpha1:hGFP+ and E/nestin:enhanced (E)GFP+ cells expressed betaIII-tubulin or microtubule-associated protein-2; many incorporated bromodeoxyuridine, indicating their genesis in vitro [11].

Chemical compound and disease context of MAP2

• In immunohistochemical staining for MAP2, the ischemic lesion in the medial CA1 maintained after 5 min ischemia and the subsequent early reperfusion period in the untreated brains was protected by the preischemic injection of 10 mg kg-1 MK-801, but was not restored by the injection of 0.5 mg kg-1 Nimodipine or 1 mg kg-1 Nicardipine [12].
• However, in the B104 rat neuroblastoma cell line the MAP2 antigen appeared to be associated with the cytoskeleton concomitant with differentiation induced by dibutyryl cyclic AMP [13].
• By densitometric quantification of the electrophoretically separated soluble proteins, mean +/- SEM MAP2 content in the hippocampus (14.4 +/- 1.8 micrograms/mg protein) was depleted (5.4 +/- 0.5 micrograms/mg, p less than 0.01) 4 days after ischemia; this depletion was significantly inhibited by 1 or 10 mg nilvadipine/kg/day [14].
• Furthermore, KB-5666 dose-dependently prevented a marked decrease in microtubule-associated protein 2 immunoreactivity in the dendritic fields of the CA1 pyramidal cells after ischemia [15].
• Selective toxicity of cocaine on neurons was paralleled by a concomitant decrease of the culture content in microtubule-associated protein 2 (MAP2), a neuronal marker measured by solid-phase immunoassay [16].

Biological context of MAP2

• Defects in the expression of MAP2 and MAP5, two proteins that contribute to the establishment and maintenance of neuronal polarity, could underlie some of the cytoarchitectural abnormalities described in schizophrenia and impair signal transduction in the affected dendrites [17].
• It is likely that the MAP2 and ERT kinases account for the phosphorylation of the EGF receptor at Thr669 observed in cultured cells [18].
• These phenotypes were accompanied by changes in the microtubule-associated proteins MAP1B and MAP2 [19].
• MspI RFLP for microtubule associated protein-2 (MAP2) [20].
• This protein exists as two isoforms of 413 and 453 amino acids with four or five tandem repeats that are 50% identical to the tau/MAP2/MAP4 repeats [21].

Anatomical context of MAP2

• MARK phosphorylates the microtubule-associated proteins tau, MAP2, and MAP4 on their microtubule-binding domain, causing their dissociation from microtubules and increased microtubule dynamics [22].
• Abnormal expression of two microtubule-associated proteins (MAP2 and MAP5) in specific subfields of the hippocampal formation in schizophrenia [17].
• In five of the six subjects with schizophrenia, prominent and specific alterations were found in the distribution of two microtubule-associated proteins, MAP2 and MAP5, which were anatomically selective for the subiculum and entorhinal cortex [17].
• The colocalization of MAP2 and tau in growth structures recapitulated their codistribution in developing neurites [23].
• Similar multimeric tubulin-binding domains in other proteins of the MAP2 class, including tau in axons and MAP4 in glial cells, may play the same role in the development and support of asymmetric cell morphology [24].

Associations of MAP2 with chemical compounds

• Specific binding of dehydroepiandrosterone to the N terminus of the microtubule-associated protein MAP2 [25].
• The expression of this polypeptide in cultured cell lines led to a rearrangement of the microtubules in a pattern distinct from that produced by MAP2 or tau, and increased their resistance to treatment with the microtubule depolymerising agent nocodazole [26].
• Interestingly, there is a noteworthy up-regulation of somatodendritic MAPs such as high-molecular-weight MAP2 and mode II-phosphorylated MAP1B in neurons cultured on stably transfected 3T3 cells overexpressing ephrin-B1 compared with neurons plated on either control 3T3 cells or poly-L-lysine [27].
• 5. These tau species although having other Ser/Thr-Pro motifs susceptible of phosphorylation by proline-directed protein kinases are not further phosphorylated in vitro by MAP2 kinase whereas the fraction isolated at pH 7.0, which contains underphosphorylated tau species, is phosphorylated [28].
• The MAP2 kinase had an apparent molecular mass of about 40 kDa as determined by gel filtration and by sucrose density gradient centrifugation [29].

Physical interactions of MAP2

• Non-neuronal 210 x 10(3) Mr microtubule-associated protein (MAP4) contains a domain homologous to the microtubule-binding domains of neuronal MAP2 and tau [30].
• Phosphorylation of the regulatory subunit of type II beta cAMP-dependent protein kinase by cyclin B/p34cdc2 kinase impairs its binding to microtubule-associated protein 2 [31].
• Additionally, both tau and MAP-2 co-precipitated with PLC-gamma [32].
• Microtubule-associated protein 2 (MAP-2) is an abundant neuronal cytoskeletal protein that binds to tubulin and stabilizes microtubules [33].

Enzymatic interactions of MAP2

• Enzyme-linked immunosorbent assays confirmed the interaction between the SH2 domain of Grb2 and a tyrosine-phosphorylated MAP-2 peptide spanning the pY(67)SN motif [34].

Co-localisations of MAP2

• Furthermore, MAP-2 was co-localized with alpha-synuclein and ubiquitin in cytoplasmic LBs of neurons [35].

Regulatory relationships of MAP2

• Interestingly, the EGF-stimulated MAP2 kinase activity was sensitive to micromolar concentrations of free Ca2+; it was inhibited 50% by 0.5 microM Ca2+ and almost totally inhibited by 2 microM Ca2+ [36].
• Spindle-shaped cells not associated with the chains were labeled for the PDGF-alpha receptor and often coexpressed MAP2 neuronal isoforms [37].
• Overexpression of CPEB in neurons promotes the transport of CPE-containing endogenous MAP2 mRNA to dendrites, whereas overexpression of a mutant CPEB that is defective for interaction with molecular motors inhibits this transport [38].
• Mapmodulin inhibits the initial rate of MAP2 binding to microtubules, a property that may allow mapmodulin to displace MAPs from the path of organelles translocating along microtubules [39].
• Treatment of peripheral blood neutrophils or terminally differentiated HL-60 cells with GM-CSF induced a rapid and dose-dependent increase in MAP2 kinase activity [40].

Other interactions of MAP2

• Double-immunolabelling for poly(ADP-ribose) and markers of neuronal, astrocytic and microglial differentiation (MAP2, GFAP and CD68, respectively) showed many of the cells containing poly(ADP-ribose) to be neurons [41].
• To date, only two MAP family members, MAP1A and MAP2, have been well characterized and studied in mammals [42].
• Double fluorescent laser scanning microscopy showed that GFAP and MAP2 labeled different tumor cell populations [3].
• Immunoblots confirmed a loss of MAP2 and MAP1B within a few hours after death [43].
• These neuronal precursors expressed betaIII tubulin, the dendritic marker MAP2 and the presynaptic marker synaptophysin after 7 days of in vitro maturation [44].

Analytical, diagnostic and therapeutic context of MAP2

• To evaluate the role of charged residues in these modules as potential morphology-specifying elements, we used site-directed mutagenesis to replace selected residues within the MAP2 MTBR by residues at corresponding positions in Tau [45].
• In this study, double-label immunocytochemistry was used to clarify the relationship between the appearance of neurofibrillary pathology (NTs and NFTs) and the loss of normal cytoskeletal components, such as microtubule-associated protein 2 (MAP2) in 13 AD cases and 6 nondemented elderly control individuals [46].
• All tumors were immunoreactive for class III beta-tubulin and MAP2, which were seen in cytoskeletal structures by immunoelectron microscopy [47].
• The transient decreases in MAP2 and tau immunoreactivity did not reflect alterations in protein levels measured using immunoblotting [48].
• These data point towards MAP2 as valuable diagnostic tool for pattern recognition and differential diagnosis of low-grade neuroepithelial tumors [49].

References