Characterization of the Microtubule-binding Domain of Microtubule-associated Protein 1A and Its Effects on Microtubule Dynamics

Vaillant, Andrew; Müller, Rachel; Langkopf, Anja; Brown, David L.

doi:10.1074/jbc.273.22.13973

Cited by 28 publications

(31 citation statements)

References 34 publications

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“…In contrast to the other members of the family, MAP1S hardly contains any extra sequences in addition to the conserved hallmark domains MH1, MH2, and MH3. Most notably, MAP1S does not contain heavy chain domains that were implicated in microtubule binding of MAP1A (27,28) and MAP1B (29). Consistent with this observation, we found only one microtubule-binding domain in MAP1S that is located in the NH 2 terminus of the light chain (Fig.…”

Section: Discussionsupporting

confidence: 76%

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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Section: Discussionsupporting

confidence: 76%

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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“…As is the case with MAP1B, both the highly basic repeats and their flanking regions are important for microtubule binding (Vaillant et al, 1998). Transfection experiments suggest that MAP1A stabilises microtubules but does not bundle them (Vaillant et al, 1998). The highly basic MAP1B/1A repeat motif is also found in otherwise apparently unrelated proteins.…”

Section: Molecular Propertiesmentioning

confidence: 95%

“…MAP1A forms a heterotetrameric complex in vivo consisting of the heavy chain, and light chains 1, 2, and 3 (Kuznetsov et al, 1986;Schoenfeld et al, 1989). As is the case with MAP1B, both the highly basic repeats and their flanking regions are important for microtubule binding (Vaillant et al, 1998). Transfection experiments suggest that MAP1A stabilises microtubules but does not bundle them (Vaillant et al, 1998).…”

Section: Molecular Propertiesmentioning

confidence: 97%

MAP1B expression and microtubule stability in growing and regenerating axons

Gordon‐Weeks

Fischer

2000

Microsc. Res. Tech.

113

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MAP1B is a microtubule‐associated phosphoprotein that is particularly highly expressed in developing neurons. There is experimental evidence that it plays an important role in neuronal differentiation, especially the extension of axons and dendrites, but exactly what role is unclear. Recent experiments have shed light on the gene structure of MAP1B and identified some of the kinases that phosphorylate the protein. Implicit in these findings is the idea that MAP1B regulates the organisation of microtubules in neurites and is itself regulated in a complex way and at a number of levels. Microsc. Res. Tech. 48:63–74, 2000. © 2000 Wiley‐Liss, Inc.

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“…For example, the heat-stable structural MAPs (including Tau, MAP2, and MAP4) utilize a MT-binding region in their carboxyl termini that consists of a proline-rich region, an inter-repeat (IR) region, and either three or four repeats of 31 amino acids Lee and Rook, 1992;Ferralli et al, 1994]. MAP1A and MAP1B proteins contain a basic region in their amino termini that binds MTs [Noble et al, 1989;Vaillant et al, 1998], although the lightchain region of MAP1B also has MT binding capacity, which is not shared in the homologous region of MAP1A [Togel et al, 1998;Noiges et al, 2002]. The Dis1/TOG family member XMAP215 uses amino and carboxyl regions for MT stabilization and binding, respectively, although the repeats contained in these proteins do not correspond to known MT-binding motifs [Ohkura et al, 2001;Popov et al, 2001].…”

Section: Introductionmentioning

confidence: 98%

CLAMP, a novel microtubule-associated protein with EB-type calponin homology

Dougherty

Adler

Rzadzinska

et al. 2005

Cell Motil. Cytoskeleton

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Microtubules (MTs) are polymers of alpha and beta tubulin dimers that mediate many cellular functions, including the establishment and maintenance of cell shape. The dynamic properties of MTs may be influenced by tubulin isotype, posttranslational modifications of tubulin, and interaction with microtubule-associated proteins (MAPs). End-binding (EB) family proteins affect MT dynamics by stabilizing MTs, and are the only MAPs reported that bind MTs via a calponin-homology (CH) domain (J Biol Chem 278 (2003) 49721-49731; J Cell Biol 149 (2000) 761-766). Here, we describe a novel 27 kDa protein identified from an inner ear organ of Corti library. Structural homology modeling demonstrates a CH domain in this protein similar to EB proteins. Northern and Western blottings confirmed expression of this gene in other tissues, including brain, lung, and testis. In the organ of Corti, this protein localized throughout distinctively large and well-ordered MT bundles that support the elongated body of mechanically stiff pillar cells of the auditory sensory epithelium. When ectopically expressed in Cos-7 cells, this protein localized along cytoplasmic MTs, promoted MT bundling, and efficiently stabilized MTs against depolymerization in response to high concentration of nocodazole and cold temperature. We propose that this protein, designated CLAMP, is a novel MAP and represents a new member of the CH domain protein family.

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Characterization of the Microtubule-binding Domain of Microtubule-associated Protein 1A and Its Effects on Microtubule Dynamics

Cited by 28 publications

References 34 publications

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

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

MAP1B expression and microtubule stability in growing and regenerating axons

CLAMP, a novel microtubule-associated protein with EB-type calponin homology

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