Disease relevance of Mtap1b

• In differentiated neuroblastoma cells, only MAP-1B and beta-tubulin are phosphorylated in a manner coupled to neurite outgrowth [1].
• However, levels of two target-encoded proteins, an L-type calcium channel subunit and MAP1B, were downregulated in specific brain regions suggesting a defect in the expression of target-encoded proteins in fragile X syndrome [2].
• MeWo melanoma cells (clone LC1) secrete a potent mitogenic activity susceptible to reinitiate DNA replication in quiescent rodent fibroblasts (CCL39, NRK-49F, NIH-3T3) but not in BHK-21 kidney cells [3].
• In order to further investigate the role of MAP1B during axonogenesis we have cultured dorsal root ganglion (DRG) neurons from a MAP1B deficient mutant mouse [4].

Psychiatry related information on Mtap1b

• Using the multiple T-maze, the open field and the Morris water maze we found that mice homozygous for a deletion of the MAP1B gene demonstrate impaired locomotor activity most likely correlated to a lack of physical endurance in general [5].

High impact information on Mtap1b

• To investigate this we have assessed neutrophil transmigration both in vivo and in vitro and examined the content and subcellular distribution of LC1 in PMNs by fluorescence-activated cell-sorting (FACS) analysis, western blotting and confocal microscopy [6].
• We report that LC1 is mobilized and externalized following PMN adhesion to endothelial monolayers in vitro or to venular endothelium in vivo and that the end point of this process is a negative regulation of PMN transendothelial passage [6].
• A permanent L-cell variant cell line (LC1) was isolated by the growth of the parent L-cell line (L) in the presence of a cytostimulatory dose (1:200) of rabbit anti-L-cell antiserum (AL) for 9 mo [7].
• Increased microtubule stability is correlated with a decrease in GSK-3beta-mediated phosphorylation of MAP-1B [8].
• Application of a JNK inhibitor caused irregular morphology and increased stable microtubules in processes, and decreased phosphorylation of microtubule associated protein 1B, raising a possibility of the involvement of JNK in controlling tubulin dynamics in migrating neurons [9].

Biological context of Mtap1b

• 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 [10].
• The interaction between these two MAPs is regulated by the phosphorylation of MAP1B [11].
• To define the microtubule binding domain in vivo, full-length and deletion constructs encoding MAP1B were assembled and introduced into cultured cells by transfection [12].
• These phenotypes are markedly more severe in tau-/-map1b-/- double mutants, indicating that tau and MAP1B act in a synergistic fashion [13].
• Heterozygotes of our MAP1B disruption exhibit no overt abnormalities in their development and behavior, while homozygotes showed a slightly decreased brain weight and delayed nervous system development [14].

Anatomical context of Mtap1b

• Synergistic effects of MAP2 and MAP1B knockout in neuronal migration, dendritic outgrowth, and microtubule organization [10].
• In these neurons, synergistic effects caused by the loss of MAP2 and MAP1B were more apparent in dendrites than in axons [10].
• MAP1B is a neuron-specific microtubule-associated protein implicated in the crosstalk between microtubules and actin filaments [15].
• Thus, we suggest that the observed phosphorylation of a protein identified as MAP-1B during neurite outgrowth is mainly due to the activation of a casein kinase II-related activity in differentiating neuroblastoma cells [16].
• Microtubule-associated protein 1B (MAP1B), one of the microtubule-associated proteins (MAPs), is a major component of the neuronal cytoskeleton [14].

Associations of Mtap1b with chemical compounds

• On the other hand, the anticipated involvement of MAP1B in retinal development and gamma-aminobutyric acid C receptor clustering was not substantiated [17].
• Lithium induces the loss of a phosphorylated form of MAP-1B, a microtubule associated protein involved in axonal outgrowth [18].
• Heterologous cell transfection experiments with full-length MAP1B, in which either phosphorylation site was separately mutated to a valine or, in a double mutant, in which both sites were mutated, showed that these GSK-3beta phosphorylation sites contribute to the regulation of microtubule dynamics by MAP1B [19].
• A population of MAP5-positive cells was also found to incorporate BrdU; some cells expressed MAP5 within 30 min of BrdU labeling [20].
• This possibility was investigated using dissociated, cortical cells in vitro by measuring the expression of MAP5 and the neuroepithelial marker nestin, together with the incorporation of bromodeoxyuridine (BrdU), a thymidine analogue that labels the DNA of proliferating cells in the S-phase of the cell cycle [20].

Enzymatic interactions of Mtap1b

• Inhibition of GSK-3 beta leads to a decrease in a phosphorylated form of microtubule-associated protein-1B (MAP-1B), a protein involved in microtubule assembly, and a concomitant decrease in the level of stable microtubules [21].
• In brain microtubule protein, MAP-1B appears to be phosphorylated in vitro by an endogenous casein kinase II-like activity which also phosphorylates the related protein MAP-1A but scarcely phosphorylates MAP-2 [16].
• Furthermore, the phosphopeptide patterns of brain MAP-1B phosphorylated in vitro by either purified casein kinase II or an extract obtained from differentiating neuroblastoma cells are identical to each other and similar to that of in vivo phosphorylated neuroblastoma MAP-1B [16].
• An increase in the phosphorylation of microtubule-associated protein MAP-1B, which accompanies neurite outgrowth induced by serum deprivation, is also observed upon addition of the two antiprotease synthetic peptides, although the nexin-2 (amyloid) peptide induces a less marked increase in phosphorylated MAP-1B than does the nexin-1 peptide [22].

Regulatory relationships of Mtap1b

• Our primary culture studies showed an involvement of Cdk5 in regulating microtubule dynamics without affecting MAP1B phosphorylation status [23].
• We demonstrated that, as is the case when Pes1 expression is depleted by shRNA, overexpression of Mtap1b-LC1 resulted in diminished proliferation of NIH3T3 cells, suggesting that Mtap1b-LC1 has the potential to repress cell proliferation by modulating the nucleolar levels of Pes1 [24].

Co-localisations of Mtap1b

• In PC12 cells, GAPDH was found in cytoplasm and nuclei and partially co-localized with MAP1B [25].

Other interactions of Mtap1b

• MAP1B and MAP2 are major members of neuronal microtubule-associated proteins (MAPs) [10].
• MAP1B is required for Netrin 1 signaling in neuronal migration and axonal guidance [15].
• Our results indicate that, in hippocampal neurons, MAP1B and LIS1 co-localize, associate and interact with each another [11].
• There was also increased expression of phosphorylated high molecular weight neurofilament subunit (NF-H), NF-M, and MAP1B [26].
• Additional genetic linkage studies of markers not informative in the A/J x C57BL/6J cross positioned D13Mit30, -72, -195, and -203, D13Gor4, D13Hun35, and Mtap5 in the immediate vicinity of the Lgn1 locus [27].

Analytical, diagnostic and therapeutic context of Mtap1b

• To better define the role of MAP1B in vivo, we have used gene targeting to disrupt the murine MAP1B gene [14].
• The expression of transfected polypeptides was monitored by indirect immunofluorescence using anti-MAP1B-specific antisera [12].
• A neuroblastoma protein related to the brain microtubule-associated protein, MAP-1B, as determined by immunoprecipitation and coassembly with brain microtubules, becomes phosphorylated when N2A mouse neuroblastoma cells are induced to generate microtubule-containing neurites [16].
• Immunoblotting of the pituitary MAP fraction revealed the presence of appreciable quantities of MAP 1A, MAP 1B, and MAP 2 polypeptides [28].
• Molecular cloning of microtubule-associated protein 1 (MAP1A) and microtubule-associated protein 5 (MAP1B): identification of distinct genes and their differential expression in developing brain [29].

References