Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.11.18 (MAP)
 7,412 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Microtubule-associated protein IB (MAP1B) is the first MAP to be detected in the developing nervous system, and it becomes markedly down-regulated postnatally. Its expression, particularly that of its phosphorylated isoform, is associated with axonal growth. To determine whether adult central nervous system (CNS) areas that retain immunoreactivity for MAP1B are associated with morphological plasticity, we compared the distribution of a phosphorylated MAP1B isoform (MAP1B-P) to the distribution of total MAP1B protein and MAP1B-mRNA. Although they were present only at very low levels, both protein and message were found ubiquitously in almost all adult CNS neurons. The intensity of staining, however, varied markedly among different regions, with only a few nuclei retaining relatively high levels. MAP1B-P was restricted to axons, whereas total MAP1B was present in cell bodies and processes. Relatively to total MAP1B protein and its mRNA, MAP1B-P levels decreased more dramatically with maturation, and they were detectable in only a few specific areas that underwent structural modifications. These included primary afferents and motor neurons, olfactory tubercles, habenular and raphe projections to interpeduncular nuclei, septum, and the hypothalamus. The distribution pattern of MAP1B-P was compared to that of the embryonic N-CAM rich in polysialic acid (PSA-NCAM). We found that the PSA-NCAM immunostaining was largely overlapped with that of MAP1B-P in the adult CNS. These results suggest that, like PSA-NCAM, MAP1B may be one of the molecules expressed during brain development that also plays a role in structural remodeling in the adult.
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PMID:Expression of a phosphorylated isoform of MAP1B is maintained in adult central nervous system areas that retain capacity for structural plasticity. 872 42

Protein function in vivo can be studied by deleting (knock-out) the gene that encodes it, and search for the consequences. This procedure involves different technologies, including recombinant DNA procedures, cell biology methods and histological and immunocytochemical analysis. In this work we have reviewed these procedures when they have been applied to ascertain the function of several microtubule-associated proteins. These proteins have been previously involved, through in vitro experiments, in having a role in the microtubule stabilization. Here, we will summarize the generation and characterization of different microtubule-associated protein knock-out mice. Special attention will be paid to MAP1B knock-out mice. Amongst the different MAPs knock-out mice these show the strongest phenotype, the most likely for being MAP1B, the MAP that is expressed earliest in neurogenesis. Molecular genetics could be considered as a valid and useful procedure to truly establish the in vivo functions of a protein, although it is necessary to be aware of possible artifacts such as the generation of some kinds of RNA alternative splicing. To avoid this the best strategy to be used must consider the deletion of the exon that contains the functional domains of the protein.
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PMID:Molecular genetic approaches to microtubule-associated protein function. 1100 43

Neuronal process extension is dependent on the reorganisation of the cytoskeleton, in particular microtubules and microfilaments, and one of the ways in which microtubules are regulated is by a group of microtubule-associated proteins called MAPs. MAP1B, the first MAP to be expressed in developing neurons, has been shown to play an important role during axonogenesis. Previously, we have shown that a phosphorylated isoform of MAP1B is involved in maintaining growth cone microtubules in a dynamically unstable state. 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. These mice express only trace amounts of MAP1B, have defects in the development of their nervous system and die perinatally. Cultured DRG neurons from MAP1B deficient mice show a reduction in axon elongation and an increase in growth cone area. The reduction in axon elongation is most likely to occur due to an inhibition in the early stages of axonogenesis. Using time-lapse video we have verified that during the first 2 h after plating, MAP1B deficient neurones extend their axons with an average speed that is half the speed of control neurones. These results support the participation of MAP1B during the initial stages of axonogenesis.
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PMID:Microtubule-associated protein 1B is involved in the initial stages of axonogenesis in peripheral nervous system cultured neurons. 1208 39

The expression patterns of three microtubule-associated proteins (MAP1A, MAP1B, and MAP2A&B) were investigated in the developing optic tectum. Expression of MAP1B and middle-molecular-weight peptide of neurofilament (NF-M) was first observed in the same mesencephalic cells on day 3 of incubation, indicating that neuroblasts had been produced. At day 5, MAP1A and MAP2A&B expression appeared in the cellular layer containing the first neuroblasts that differentiate into large multipolar cells. The NF-M+ neurites in the striatum album centrale (SAC) and the striatum opticum (SO) were MAP1B+ up to day 19, but the intensity of MAP1B immunoreactivity decreased with development. All three MAPs were expressed in large multipolar neurons in the developing stratum griseum centrale from the beginning of maturation. Stratum griseum et fibrosum centrale cellular layers, containing radially arranged piriform neurons, were MAP1A-/MAP2A&B- on day 11 but became MAP1A+/MAP2A&B+ during later stages. These results suggest that the timing of MAP expression in neuronal maturation of large multipolar cells differs from that of piriform cells. The expression of MAPs has revealed specific cellular events in the developing optic tectum. Based on our observations, the development of the optic tectum can be divided into four periods.
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PMID:Distribution of MAP1A, MAP1B, and MAP2A&B during layer formation in the optic tectum of developing chick embryos. 1452 40

Microtubule-associated protein 1B is the first MAP to be expressed during the development of the nervous system. Several different approaches have revealed that MAP1B function is associated with microtubule and actin microfilament polymerization and dynamics. In recent years, the generation of molecular models to inactivate MAP1B function in invertebrates and mammals has sparked some controversy about the real role of MAP1B. Despite discrepancies between some studies, it is clear that MAP1B plays a principal role in the development of the nervous system. In this article, we summarize the evidence for MAP1B function in a wide variety of cellular processes implicated in the proper construction of the nervous system. We also discuss the role of MAP1B in pathological processes.
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PMID:Microtubule-associated protein 1B function during normal development, regeneration, and pathological conditions in the nervous system. 1459 69

For neuronal migration to occur, the cell must undergo morphological changes that require modifications of the cytoskeleton. Several different MAPs (microtubule-associated proteins) or actin-binding proteins are proposed to be involved in the migration of neurons. Therefore we have specifically analysed how two members of the MAP family, MAP1B and LIS1 (lissencephaly-related protein 1), interact with one another and participate in neuronal migration. Our results indicate that, in hippocampal neurons, MAP1B and LIS1 co-localize, associate and interact with each another. The interaction between these two MAPs is regulated by the phosphorylation of MAP1B. Furthermore, this interaction interferes with the association between LIS1 and the microtubule-dependent molecular motor, dynein. Clearly, the differential binding of these cytoskeletal proteins could regulate the functions attributed to the LIS1-dynein complex, including those related to extension of the neural processes necessary for neuronal migration.
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PMID:Binding of microtubule-associated protein 1B to LIS1 affects the interaction between dynein and LIS1. 1576 42

The MAPs (microtubule-associated proteins) MAP1B and tau are well known for binding to microtubules and stabilizing these structures. An additional role for MAPs has emerged recently where they appear to participate in the regulation of transport of cargos on the microtubules found in axons. In this role, tau has been associated with the regulation of anterograde axonal transport. We now report that MAP1B is associated with the regulation of retrograde axonal transport of mitochondria. This finding potentially provides precise control of axonal transport by MAPs at several levels: controlling the anterograde or retrograde direction of transport depending on the type of MAP involved, controlling the speed of transport and controlling the stability of the microtubule tracks upon which transport occurs.
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PMID:Role of MAP1B in axonal retrograde transport of mitochondria. 1653 27

Spinal cord injury (SCI) results in loss of sensory and motor function because injured axons do not regenerate and neurons that die are not replaced. Nevertheless, there is evidence for spontaneous reorganization of spared pathways (i.e. sprouting) that could be exploited to improve functional recovery. The extent of morphological remodeling after spinal cord injury is, however, not understood. We have previously shown that a phosphorylated form of microtubule-associated protein-1B, MAP1B-P, is expressed by growing axons, but is detected in intact adult SC in fibers exhibiting a somatotopic distribution of myelinated sensory fibers. We now demonstrate that after adult SCI, MAP1B-P is up-regulated in other classes of axons. We used immunohistochemistry to show changing levels and distributions of MAP1B-P after a right thoracic hemisection of adult rat spinal cord. MAP1B-P labeling suggests rearrangements of the axonal circuitry that go well beyond previous descriptions. MAP1B-P-positive fibers are present in ectopic locations in gray matter in both dorsal and ventral horns and around the central canal. Double staining reveals that primary sensory and descending serotonergic and corticospinal axons are MAP1B-P positive. In white matter, high MAP1B-P expression is found on terminal enlargements near the injury, reflecting retraction of transected axons. MAP1B-P also accumulates in pre-apoptotic neuronal somata axotomized by the lesion, indicating association of MAP1B-P not only with axon extension and retraction, but also with neuronal degeneration. Finally, we provide evidence that MAP1B phosphorylation is correlated with activation of JNK MAP-kinase, providing a step towards unraveling the mechanisms of regulation of this plasticity-related cytoskeletal protein.
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PMID:Extensive structural remodeling of the injured spinal cord revealed by phosphorylated MAP1B in sprouting axons and degenerating neurons. 1788 Mar 87

MAP1B, a structural microtubule (MT)-associated protein highly expressed in developing neurons, plays a key role in neurite and axon extension. However, not all molecular mechanisms by which MAP1B controls MT dynamics during these processes have been revealed. Here, we show that MAP1B interacts directly with EB1 and EB3 (EBs), two core 'microtubule plus-end tracking proteins' (+TIPs), and sequesters them in the cytosol of developing neuronal cells. MAP1B overexpression reduces EBs binding to plus-ends, whereas MAP1B downregulation increases binding of EBs to MTs. These alterations in EBs behaviour lead to changes in MT dynamics, in particular overstabilization and looping, in growth cones of MAP1B-deficient neurons. This contributes to growth cone remodelling and a delay in axon outgrowth. Together, our findings define a new and crucial role of MAP1B as a direct regulator of EBs function and MT dynamics during neurite and axon extension. Our data provide a new layer of MT regulation: a classical MAP, which binds to the MT lattice and not to the end, controls effective concentration of core +TIPs thereby regulating MTs at their plus-ends.
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PMID:MAP1B regulates microtubule dynamics by sequestering EB1/3 in the cytosol of developing neuronal cells. 2357 79