The Microtubule-Associated Protein MAP1B Is Involved in Local Stabilization of Turning Growth Cones

Mack, Till G. A.; Koester, Michael P.; Pollerberg, G. Elisabeth

doi:10.1006/mcne.1999.0802

Cited by 85 publications

(83 citation statements)

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“…The activity-regulated localization of FMRP into dendrites and spines (36) further implicates the possibility for FMRP to regulate translation of MAP1B and microtubule dynamics within the individual dendrite and͞or synapse, perhaps in response to neurotransmitter release. Considering the critical roles of microtubule dynamics in the development of neuronal networks, particularly in growth cone dynamics and synapse formation (32,(37)(38)(39)(40), abnormal microtubule dynamics caused by FMRP deficiency provides a conceivable mechanism underlying the abnormalities in structural synaptic plasticity in fragile X mental retardation, represented by the delayed dendritic spine maturation in vivo (6) and the deficits in synapse formation in primary cultured neurons (41).…”

Section: Discussionmentioning

confidence: 99%

The fragile X protein controls microtubule-associated protein 1B translation and microtubule stability in brain neuron development

Wang

Liang

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

283

265

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The fragile X mental retardation protein (FMRP) is a selective RNA-binding protein implicated in regulating translation of its mRNA ligands. The absence of FMRP results in fragile X syndrome, one of the leading causes of inherited mental retardation. Delayed dendritic spine maturation was found in fragile X mental retardation patients as well as in Fmr1 knockout (KO) mice, indicating the functional requirement of FMRP in synaptic development. However, the biochemical link between FMRP deficiency and the neuronal impairment during brain development has not been defined. How FMRP governs normal synapse development in the brain remains elusive. We report here that the developmentally programmed FMRP expression represses the translation of microtubule associated protein 1B (MAP1B) and is required for the accelerated decline of MAP1B during active synaptogenesis in neonatal brain development. The lack of FMRP results in misregulated MAP1B translation and delayed MAP1B decline in the Fmr1 KO brain. Furthermore, the aberrantly elevated MAP1B protein expression leads to abnormally increased microtubule stability in Fmr1 KO neurons. Together, these results indicate that FMRP plays critical roles in controlling cytoskeleton organization during neuronal development, and the abnormal microtubule dynamics is a conceivable underlying factor for the pathogenesis of fragile X mental retardation.T he absence of fragile X mental retardation protein (FMRP), a messenger ribonucleoprotein (mRNP) associated with a subclass of brain mRNAs, results in fragile X mental retardation, affecting 1 in 4,000 males and 1 in 8,000 females (1-3). The lack of FMRP results in delayed dendritic spine maturation in fragile X patients as well as in Fmr1 knockout (KO) mice (4-8), indicating the essential role of FMRP in synapse development. Furthermore, the association of FMRP with translating polyribosomes (9-12) and micro-RNA machinery (13) suggests that FMRP governs translation efficiency of its mRNA targets, which in turn modulates synaptic development and plasticity.FMRP has been shown to act as a translation repressor for its associated mRNAs in vitro as well as in cultured cell lines (14-17). To date, Ͼ400 mRNAs have been identified to associate with FMRP in vivo (18-21). In fragile X patient cells and synaptoneurosomes isolated from the Fmr1 KO brain, the lack of FMRP causes abnormal polyribosome-association of several mRNAs that normally bind to FMRP (18,21). Consistent with the proposed function of FMRP in regulating translation in synaptic plasticity, activity-dependent production of the synaptic protein PSD95 is abrogated in the Fmr1 KO primary neuronal cultures (22). In addition, the mRNA of the microtubuleassociated protein 1B (MAP1B), a neuronal MAP playing principle roles in neurite and synapse development (23), is a predicted target of FMRP (18,19,21). Interestingly, deficiency of Drosophila Fmr1 (dFmr1) results in abnormally elevated expression of the microtubule associated protein Futsch and synaptic over growth at the neuromuscular...

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Section: Discussionmentioning

confidence: 99%

The fragile X protein controls microtubule-associated protein 1B translation and microtubule stability in brain neuron development

Wang

Liang

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

283

265

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“…Total RNA (5 g) was reverse-transcribed using oligo(dT) [12][13][14][15][16][17][18] and Superscript II Reverse Transcriptase (Invitrogen) and subsequently amplified by PCR using primers 5Ј-ACGAAT-TCTGGTGGTGGGTGGCGAGTGTGG-3Ј and 5Ј-ACGAATTCAACAGT-GCCCAGTCCCCAAAGG-3Ј and Taq DNA polymerase (Invitrogen) according to the manufacturer's instructions. 5 l of the reaction were analyzed on agarose gels.…”

Section: Reverse Transcription-pcr Analysis Of Map1s Expressionmentioning

confidence: 99%

“…Together, these observations suggest that MAP1B and perhaps MAP1A regulate the cytoskeleton in response to extracellular guidance cues to permit axon extension and growth cone turning. This view is supported by the finding that changes in the activity of serinethreonine kinases casein kinase II, glycogen synthase kinase-3␤, and cyclin-dependent kinase 5 lead to altered MAP1B phosphorylation (13)(14)(15) and by the fact that local inactivation of MAP1B on one side of the growth cone induces growth cone turning (16). On the other hand, there is evidence that the function of MAP1B and perhaps MAP1A goes beyond regulation of the neuronal cytoskeleton.…”

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confidence: 96%

Microtubule-associated Protein 1S, a Short and Ubiquitously Expressed Member of the Microtubule-associated Protein 1 Family

Orbán-Németh

Simader

Badurek

et al. 2005

Journal of Biological Chemistry

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The related high molecular mass microtubuleassociated proteins (MAPs) MAP1A and MAP1B are predominantly expressed in the nervous system and are involved in axon guidance and synaptic function. MAP1B is implicated in fragile X mental retardation, giant axonal neuropathy, and ataxia type 1. We report the functional characterization of a novel member of the microtubule-associated protein 1 family, which we termed MAP1S (corresponding to sequence data bank entries for VCY2IP1 and C19ORF5). MAP1S contains the three hallmark domains of the microtubuleassociated protein 1 family but hardly any additional sequences. It decorates neuronal microtubules and copurifies with tubulin from brain. MAP1S is synthesized as a precursor protein that is partially cleaved into heavy and light chains in a tissue-specific manner. Heavy and light chains interact to form the MAP1S complex. The light chain binds, bundles, and stabilizes microtubules and binds to actin. The heavy chain appears to regulate light chain activity. In contrast to MAP1A and MAP1B, MAP1S is expressed in a wide range of tissues in addition to neurons and represents the non-neuronal counterpart of this cytolinker family.The classical microtubule-associated proteins (MAPs) 1 MAP1, MAP2, and tau were discovered more than 20 years ago by virtue of the fact that they copurified with microtubules from vertebrate brain (1). Because of the developmental regulation of expression of these proteins, their restricted localization in the axonal or somato-dendritic compartment of neurons, and the differential phosphorylation depending on the developmental stage and subcellular localization, it was soon proposed that MAPs are important regulators of neuronal microtubules during differentiation.The MAP1 family has two members: MAP1A and MAP1B. Both proteins are of high molecular mass (ϳ300 kDa, 2500 aa), are expressed predominantly in the nervous system, and consist of several subunits, one heavy chain (HC) and at least one light chain (LC) (1). In each case, heavy and light chains are the products of proteolytic cleavage of a common polyprotein precursor. MAP1A and MAP1B share three substantial regions of sequence homology (2), one in the NH 2 terminus of the heavy chains, one in the COOH terminus of the heavy chains, and one in the COOH-terminal half of the light chains. We termed these homologous hallmark domains of the MAP1 family MH1, MH2, and MH3, respectively. In MAP1B, the MH1 and MH3 domains mediate the interaction between heavy and light chains (3), and the MH3 domain of both proteins contains an actin binding site (4). MAP1A and MAP1B are conserved in vertebrates. A MAP1 ortholog termed Futsch has been identified in Drosophila (5).MAP1B function has been investigated by gene targeting in the mouse, and the original contention that it is important for neuronal differentiation and development of the nervous system has been confirmed (6 -9). Mice homozygous for hypomorphic or null alleles of MAP1B display defects in axonal guidance, neuronal migration, axon diameter, and ...

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“…Besides the widely used stripe assay consisting of straight individual stripes, other geometric patterns-such as zig-zag patterns-have been employed 29 . These zig-zag stripes are valuable when analyzing cell behavior and signal-transduction events at substrate borders, where, for example, one part of a cell is adhering to a laminin substrate and the other part is contacting a substrate of different molecular nature 30 .…”

Section: Introductionmentioning

confidence: 99%

Stripe assay to examine axonal guidance and cell migration

et al. 2007

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Stripe assays have been widely employed as in vitro test systems to study the responses of growing axons, as well as migrating cells, to established or novel guidance molecules. We provide detailed protocols for both the original and the modified version of this assay, as they allow the analysis of the 'guidance properties' of active components present in crude membrane fractions or as purified molecules. Silicon matrices are used to produce striped patterns of active molecules on a surface (referred to as 'carpet'), followed by culturing of neurons, or any other cell type, on these carpets. After 1-2 days in culture, striped outgrowth of extending neuritesindicative of guided migration of cell processes-can be observed. We also discuss potential other applications (e.g., in neuronal regeneration and development) and modifications of the assay. The preparation of 10-12 carpets takes approximately 4-5 h. INTRODUCTIONThe stripe assay was originally designed by F. Bonhoeffer and co-workers 1,2 in the late 1980s to analyze fundamental axonal guidance mechanisms governing the formation of the topographic map established in the chick retino-tectal system (for review, see ref.3). Employing this assay, the presence of a graded distribution of repulsive axon guidance cues, present predominantly in posterior tectal membranes, was discovered. Subsequently, this assay was modified, permitting the identification of ephrin-As as the key components present in posterior membranes that are responsible for the repulsive properties 4-7 .The stripe assay has since been used to uncover guidance cues and mechanisms in many principal neuronal projections, including, for example, the hippocampal, thalamic and olfactory systems [8][9][10][11] . The stripe assay was also applied to investigate neurite outgrowth and guidance behavior related to neuronal regeneration 12-15 and branch formation 16 . Furthermore, the stripe assay has proven valuable in dissecting signaling cascades initiated downstream of axonal guidance receptors activated by ligands printed in a striped pattern [12][13][14][15] . In addition, the guidance properties of membrane-tethered molecules as well as the short-range action of secreted guidance molecules (such as Slits and Semaphorins) could be mimicked in vitro by this assay 17,18 . Also stripe assay experiments were conducted to unravel potential guidance properties of extracellular matrix components 19,20 and of cell adhesion molecules of the IgG superfamily 21 .Of note, the stripe assay was employed as an in vitro assay to investigate the navigation responses of both axonal growth cones toward guidance cues and of migrating cells 4,22,23 . With respect to the latter, neural crest cells 22 and oligodendrocytes 23,24 , but also non-neuronal cells such as tumor cells, have been studied 25 .The assay allows assessment of guidance activity of established molecules and also testing potential guidance properties of hitherto uncharacterized molecules such as RGM, the Wnt signaling inhibitor SFRP1 or the morphogen Sonic h...

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The Microtubule-Associated Protein MAP1B Is Involved in Local Stabilization of Turning Growth Cones

Cited by 85 publications

References 83 publications

The fragile X protein controls microtubule-associated protein 1B translation and microtubule stability in brain neuron development

The fragile X protein controls microtubule-associated protein 1B translation and microtubule stability in brain neuron development

Microtubule-associated Protein 1S, a Short and Ubiquitously Expressed Member of the Microtubule-associated Protein 1 Family

Stripe assay to examine axonal guidance and cell migration

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