Non-motor microtubule-associated proteins

doi:10.1016/S0955-0674(05)80013-4

Current Opinion in Cell Biology

Volume 5, Issue 1, February 1993, Pages 88-91

https://doi.org/10.1016/S0955-0674(05)80013-4 Get rights and content

This past year, the structure and function of microtubule-associated proteins (MAPs) have been investigated in studies probing their phosphorylation, patterns of expression, and the function of the microtubule-binding domain. Cellular studies have also contributed new insights into the roles of these proteins in process outgrowth.

References and recommended reading (62)

GoedertM et al.
Molecular Characterization of Microtubule-associated Proteins Tau and MAP2
Trends Neurosci
(1991)
AiZAWAH et al.
Functional Analyses of the Domain Structure of Microtubule-associated Protein-4 (MAP-U)
J Biol Chem
(1991)
DrechselDN et al.
Modulation of the Dynamic Instability of Tubulin Assembly by the Microtubule Associated Protein Tau
Mol Biol Cell
(1992)
SteinerB et al.
Phosphorylation of Microtubule-associated Protein Tau: Identification of the Site for Ca²⁺calmodulin Dependent Kinase and Relationship with Tau Phosphorylation in Alzheimer Tangles
EMBO J
(1990)
IshiguroK et al.
Tau Protein Kinase I Converts Normal Tau Protein into A68-like Component of Paired Helical Filaments
J Biol Chem
(1992)
RoderHM et al.
Two Novel Kinases Phosphorylate Tau and the KSP Site of Heavy neurofilament Subunits in High Stoichiometric Ratios
J Neurosci
(1991)
HasegawaM et al.
Protein Sequence and Mass Spectrometric Analyses of Tau in the Alzheimer's Disease Brain
J Biol Chem
(1992)
WischikCM et al.
Isolation of a Fragment of Tau Derived from the Core of the Paired Helical Filament of Alzheimer Disease
KondoJ et al.
The Carboxyl Third of Tau is Tightly Bound to Paired Helical Filaments
Neuron
(1988)
KanaiY et al.
Expression of Multiple Tau Isoforms and Microtubule Bundle Formation in Fibroblasts Transfected with a Single Tau cDNA
J Cell Biol
(1989)

BaasPW et al.

Processes Induced by Tau Expression in Sf9 Cells have an Axon-like Microtubule Organization

J Cell Biol

(1991)

CaceresA et al.

Inhibition of Neunte Polarity by Tau Antisense Oligonucleotides in Primary Cerebellar Neurons

Nature

(1990)

MichalikL et al.

Microtubule Affinity Chromatography: A New Technique for Isolating Microtubulebinding Proteins from Rat Pancreas

Cell Mol Biol

(1991)

HammarbackJA et al.

MAP1B is Encoded as a Polyprotein that is Processed to Form a Complex N-terminal Microtubule-binding Domain

Neuron

(1991)

SerranoL et al.

Controlled Proteolysis of Tubulin by Subtilisin: Localization of the Site for MAP2 Interaction

Biochemistry

(1984)

LeeG

Tau Protein: An Update on Structure and Function

Cell Motil Cytoskeleton

(1990)

GoedertM et al.

Cloning of a Big Tau Microtubule-associated Protein Characteristic of the Peripheral Nervous System

CouchieD et al.

Primary Structure of High Molecular Weight Tau Present in the Peripheral Nervous System

OblingerMM et al.

tau Gene Expression in Rat Sensory Neurons During Development and Regeneration

J Neurosci

(1991)

GeorgieffIS et al.

High Molecular Weight Tau: Preferential Localization in the Peripheral Nervous System

J Cell Sci

(1991)

AndreadisA et al.

Structure and Novel Exons of the Human τGene

Biochemistry

(1992)

WestRR et al.

A Model for Microtubule-associated Protein 4 Structure. Domains Defined by Comparisons of Human, Mouse, and Bovine Sequences

J Biot Chem

(1991)

LeeG et al.

Expression of Tau Protein in Non-neuronal Cells: Microtubule Binding and Stabilization

J Cell Sci

(1992)

LewisSA et al.

Organization of Microtubules in Dendrites and Axons is Determined by a Short Hydrophobic Zipper in Microtubule-associated Proteins MAP2 and Tau

Nature

(1989)

Brandt R, Lee G: Functional Organization of Microtubuleassociated Protein Tau: Identification of Regions Which Affect...

ButnerKA et al.

Tau Protein Binds to Microtubules Through a Flexible Array of Distributed Weak Sites

J Cell Biol

(1991)

MitchisonT et al.

Dynamic Instability of Microtubule Growth

Nature

(1984)

HorioT et al.

Visualization of the Dynamic Instability of Individual Microtubules by Dark-field Microscopy

Nature

(1986)

VandreDD et al.

Proteins of the Mammalian Mitotic Spindle: Phosphorylation/Dephosphorylation of MAP-4 During Mitosis

J Cell Sci

(1991)

TombesRM et al.

Specific Association of an M-phase Kinase with Isolated Mitotic Spindles and Identification of Two of its Substrates as MAP4 and MAP1B

Cell Regul

(1991)

HoshiM et al.

Mitogen-activated-protein-kinase-catalyzed Phosphorylation of Microtubule-associated Proteins, Microtubule-associated Protein 2 and Microtubule-associated Protein 4, Induces an Alteration in their Function

Eur J Biochem

(1992)

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Tau is a neuronal protein that is associated to microtubules, together with other microtubule-associated proteins (MAPs) [139]. It is known that tau protein and the MAPs stabilize and promote the self-assembly of microtubules [140,141]. Tau also bundles actin filaments and its interactions with actin is important for neurite outgrowth [142,143].
Amyloidogenic proteins are related to a variety of amyloid diseases, such as type 2 diabetes (T2D), Alzheimer's disease (AD) and Parkinson's disease (PD). The amyloid proteins in which this review focuses include amylin, Aβ, tau and α-synuclein. Understanding the molecular mechanisms in which these amyloidogenic proteins interact with membranes is a challenging research to both experimental and computational studies. This review illustrates recent studies on amyloid-membrane interactions, but it mainly focuses on the challenge issues related to experimental techniques to investigate at the molecular level these interactions and provides thoughts and outlook for future computational studies.
Human EML4, a novel member of the EMAP family, is essential for microtubule formation
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Human EML4 (EMAP-like protein 4) is a novel microtubule-associated WD-repeat protein of 120 kDa molecular weight, which is classified as belonging to the conserved family of EMAP-like proteins. Cosedimentation assays demonstrated that EML4 associates with in vitro polymerized microtubules. Correspondingly, immunofluorescence stainings and transient expression of EGFP-labeled EML4 revealed a complete colocalization of EML4 with the interphase microtubule array of HeLa cells. We present evidence that the amino-terminal portion of EML4 (amino acids 1–249) is essential for the association with microtubules. Immunoprecipitation experiments revealed that EML4 is hyperphosphorylated on serine/threonine residues during mitosis. In addition, immunofluorescence stainings demonstrated that hyperphosphorylated EML4 is associated with the mitotic spindle, suggesting that the function of EML4 is regulated by phosphorylation. siRNA-mediated knockdown of EML4 in HeLa cells led to a significant decrease in the number of cells. In no case mitotic figures could be observed in EML4 negative HeLa cells. Additionally, we observed a significant reduction of the proliferation rate and the uptake of radioactive [³H]-thymidine as a result of EML4 silencing. Most importantly, EML4 negative cells showed a completely modified microtubule network, indicating that EML4 is necessary for correct microtubule formation.
The effects of oxidative stress and altered intracellular calcium levels on vesicular transport of apoE-EGFP
2002, Cell Biology International
Apolipoprotein E (apoE) plays a role in the distribution of lipid within many organs and cell types in the human body, including the central nervous system (CNS). The apoE4 isoform is also an established risk factor for late-onset Alzheimer's disease (AD), however its role in the aetiology of the disease remains largely unknown. Therefore, as AD is a late-onset disease, we sort to investigate how conditions hypothesised to model ageing affect apoE metabolism, such as the transport of apoE along the secretory pathway. Two of these models include oxidative stress and calcium deregulation. Using apoE-EGFP-expressing astrocytoma cell lines we established that vesicle number and velocity are up-regulated under oxidative stress conditions, and slowed under KCl induced calcium deregulation. Although these findings apply to cells in general under these two stress conditions, the up-regulation of apoE in particular may be a response to cell injury with implications for neurodegeneration such as that found with late-onset AD.
Alternative splicing of amino-terminal tau mRNA in rat spinal cord during development and following axonal injury
2001, Experimental Neurology
Tau is a family of microtubule-associated phosphoproteins in which isoform variation is produced by alternative splicing of a single gene and posttranslational modifications. Tau isoforms that include exon 10 are overexpressed in frontotemporal dementia and progressive supranuclear palsy. Therefore, we examined the expression of tau mRNA splice variants during axonal regeneration and abortive regeneration. Previous work in our laboratory demonstrated that expression of exon 10 tau isoforms during regeneration and abortive regeneration was altered and partially recapitulated the developmental patterns of tau isoform expression. Using RT-PCR, we examined the alternative splicing of exons 2 and 3 in tau during early postnatal development and regeneration in the rat spinal cord. The levels of tau lacking exons 2 and 3 were high on the day of birth and rapidly declined. Conversely, tau isoforms containing exon 2 or exons 2 and 3 first appeared at low levels and steadily increased. During axonal regeneration, the levels of all three tau mRNA isoforms were significantly lower 7 days after injury. In a model of abortive regeneration, all of the tau isoforms were elevated 14 and 42 days postinjury. The relative levels of exon 2 and 3 tau splice variants were not altered during regeneration or abortive regeneration as occurred during development. These results suggest that tau isoform expression following neuronal injury does not recapitulate the developmental pattern and is not independently regulated as in development. Our previous results together with these data suggest that alterations in tau mRNA isoform expression that occur in neurodegeneration are not secondary to axonal injury but may be a more primary event underlying cytoskeletal derangement.
Regulated association of microtubule-associated protein 2 (MAP2) with Src and Grb2: Evidence for MAP2 as a scaffolding protein
2000, Journal of Biological Chemistry
Microtubule-associated protein 2 (MAP2) and tau, which is involved in Alzheimer's disease, are major cytoskeletal proteins in neurons. These proteins are involved in microtubule assembly and stability. To further characterize MAP2, we took a strategy of identifying potential MAP2 binding partners. The low molecular weight MAP2c protein has 11 PXXP motifs that are conserved across species, and these PXXP motifs could be potential ligands for Src homology 3 (SH3) domains. We tested for MAP2 interaction with SH3 domain-containing proteins. All neuronal MAP2 isoforms bound specifically to the SH3 domains of c-Src and Grb2 in anin vitro glutathione S-transferase-SH3 pull-down assay. Interactions between endogenous proteins were confirmed by co-immunoprecipitation using brain lysate. All three proteins were also found co-expressed in neuronal cell bodies and dendrites. Surprisingly, the SH3 domain-binding site was mapped to the microtubule-binding domain that contains no PXXP motif. Src bound primarily the soluble, non-microtubule-associated MAP2c in vitro. This specific MAP2/SH3 domain interaction was inhibited by phosphorylation of MAP2c by the mitogen-activated protein kinase extracellular signal-regulated kinase 2 but not by protein kinase A. This phosphorylation-regulated association of MAP2 with proteins of intracellular signal transduction pathways suggests a possible link between cellular signaling and neuronal cytoskeleton, with MAP2 perhaps acting as a molecular scaffold upon which cytoskeleton-modifying proteins assemble and dissociate in response to neuronal activity.
Phosphorylation of microtubule-associated protein 2 (MAP2) and its relevance for the regulation of the neuronal cytoskeleton function
2000, Progress in Neurobiology
Neurons, the basic information processing units of the nervous system, are characterized by a complex polar morphology which is essential for their function. To attain their precise morphology, neurons extend cytoplasmatic processes (axons and dendrites) and establish synaptic connections in a highly regulated way. Additionally, neurons are also subjected to small plastic changes at the adult stage which serve to regulate synaptic transmission. Every step of neuronal development is genetically controlled by endogenous determinants, as well as by environmental signals including intercellular contacts, extracellular matrix and diffusible signals. Cytoskeletal components are among the main protein targets modified in response to most of those extracellular signals which ultimately determine neuronal morphology. One of the major mechanisms controlling the neuronal cytoskeleton is the modification of the phosphorylation state of cytoskeletal proteins via changes in the relative activities of protein kinases and phosphatases within neurons. In particular, the microtubule-associated protein 2 (MAP2) family of proteins is an abundant group of cytoskeletal components which are predominantly expressed in neurons and serve as substrates for most of protein kinases and phosphatases present in neurons. MAP2 phosphorylation seems to control its association with the cytoskeleton and it is developmentally regulated. Moreover, MAP2 may perform many functions including the nucleation and stabilization of microtubules (and maybe microfilaments), the regulation of organelle transport within axons and dendrites, as well as the anchorage of regulatory proteins such as protein kinases which may be important for signal transduction. These putative functions of MAP2 have also been proposed to play important roles in the outgrowth of neuronal processes, synaptic plasticity and neuronal cell death. Thus, MAP2 constitutes an interesting case to understand the regulation of neuronal function by the alteration of the phosphorylation state of cytoskeletal proteins in response to different extracellular signals. Here we will review the current knowledge about the regulation of MAP2 function through phosphorylation/dephosphorylation and its relevance in the broader context of neuronal functions.

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Non-motor microtubule-associated proteins

Trends Neurosci

J Biol Chem

Mol Biol Cell

EMBO J

J Biol Chem

J Neurosci

J Biol Chem

Neuron

J Cell Biol

J Cell Biol

Nature

Cell Mol Biol

Neuron

Biochemistry

Tau Protein: An Update on Structure and Function

Cell Motil Cytoskeleton

Cloning of a Big Tau Microtubule-associated Protein Characteristic of the Peripheral Nervous System

Primary Structure of High Molecular Weight Tau Present in the Peripheral Nervous System

tau Gene Expression in Rat Sensory Neurons During Development and Regeneration

J Neurosci

High Molecular Weight Tau: Preferential Localization in the Peripheral Nervous System

J Cell Sci

Structure and Novel Exons of the Human τGene

Biochemistry

A Model for Microtubule-associated Protein 4 Structure. Domains Defined by Comparisons of Human, Mouse, and Bovine Sequences

J Biot Chem

Expression of Tau Protein in Non-neuronal Cells: Microtubule Binding and Stabilization

J Cell Sci

Organization of Microtubules in Dendrites and Axons is Determined by a Short Hydrophobic Zipper in Microtubule-associated Proteins MAP2 and Tau

Nature

Tau Protein Binds to Microtubules Through a Flexible Array of Distributed Weak Sites

J Cell Biol

Dynamic Instability of Microtubule Growth

Nature

Visualization of the Dynamic Instability of Individual Microtubules by Dark-field Microscopy

Nature

Proteins of the Mammalian Mitotic Spindle: Phosphorylation/Dephosphorylation of MAP-4 During Mitosis

J Cell Sci

Specific Association of an M-phase Kinase with Isolated Mitotic Spindles and Identification of Two of its Substrates as MAP4 and MAP1B

Cell Regul

Mitogen-activated-protein-kinase-catalyzed Phosphorylation of Microtubule-associated Proteins, Microtubule-associated Protein 2 and Microtubule-associated Protein 4, Induces an Alteration in their Function

Eur J Biochem