Sense and antisense transfection analysis of tau function: tau influences net microtubule assembly, neurite outgrowth and neuritic stability

Esmaeli-Azad, Babak; McCarty, Joseph H.; Feinstein, Stuart C.

doi:10.1242/jcs.107.4.869

Cited by 163 publications

(31 citation statements)

References 60 publications

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“…Expression of tau has been shown to coincide with the extension of neurites during cell differentiation (Binder et al, 1985; Drubin et al, 1985; Kosik & Finch, 1987), and antisense studies indicate that tau has a role in the development and maintenance of the axon-like process of PC-12 cells (Esmaeli-Azad et al, 1994) and in the establishment of neuritic polarity in primary cerebellar neurons (Caceres & Kosik, 1990; Kosik & Caceres, 1991). Tau is also the primary component of one of the pathological hallmarks of Alzheimer's disease, the paired helical filaments [reviewed in Goedert et al (1994); Goedert et al, 1989a;Grundke-Iqbal et al, 1986].…”

mentioning

confidence: 99%

Kinetic Stabilization of Microtubule Dynamics at Steady State by Tau and Microtubule-Binding Domains of Tau

Panda¹,

Goode²,

Feinstein³

et al. 1995

Biochemistry

166

188

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Tau is a neuronal microtubule-associated protein that plays an important role in stabilizing axonal microtubules and maintaining neuronal processes. To investigate the mechanisms by which tau performs these functions, we have determined the actions of full-length adult tau and tau peptides corresponding to two different microtubule-binding domains of tau (the first repeat, R1, VRSKIGSTENLKHQPGGG, and the first interrepeat, R1-R2 IR, KVQIINKK) on the growing and shortening dynamics at the plus ends of individual microtubules at steady state. Tau suppressed steady-state microtubule dynamics at very low molar ratios of tau to tubulin. At the lowest ratios examined (tau:tubulin ratios of 1:175 and 1:85), suppression of dynamics occurred in the absence of a detectable change in polymer mass. Tau reduced the mean rate and extent of shortening and, in contrast to previous work carried out under conditions of net polymer gain, tau also suppressed the mean rate and extent of growing. Tau also strongly increased the rescue frequency, it moderately suppressed the catastrophe frequency and it strongly increased the percentage of total time that the microtubules spent in an attenuated (pause) state, neither growing nor shortening detectably. In addition, both the R1 and R1-R2 IR tau peptides suppressed steady-state microtubule dynamics in a sequence-specific manner and in a manner that was qualitatively indistinguishable from full-length tau. The data provide significant support for a mechanism in which the binding of tau to individual tubulin subunits in microtubules induces a conformational change that strengthens inter-tubulin bonding.

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mentioning

confidence: 99%

Kinetic Stabilization of Microtubule Dynamics at Steady State by Tau and Microtubule-Binding Domains of Tau

Panda¹,

Goode²,

Feinstein³

et al. 1995

Biochemistry

166

188

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“…In nondividing mature neurons, members of microtubule-associated proteins (MAPs) bind to and stabilize MTs against depolymerization. MAP Tau and MAP2 stabilize MTs in axons and dendrites, respectively. − EM studies show that MAPs may cross-bridge MTs into bundles in axons (Figure C, red arrow). , Furthermore, NF side arms have been implicated in cross-linking NFs to MTs in axons (Figure C, blue arrow). The electron micrographs of Figure , depicting coexistence of MTs and NFs, highlight the formation of the distinct cytoskeletal structures present in axons and dendrites.…”

Section: Introductionmentioning

confidence: 99%

Minireview - Microtubules and Tubulin Oligomers: Shape Transitions and Assembly by Intrinsically Disordered Protein Tau and Cationic Biomolecules

et al. 2019

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In this minireview, which is part of a special issue in honor of Jacob N. Israelachvili's remarkable research career on intermolecular forces and interfacial science, we present studies of structures, phase behavior, and forces in reaction mixtures of microtubules (MTs) and tubulin oligomers with either intrinsically disordered protein (IDP) Tau, cationic vesicles, or the polyamine spermine (4+). Bare MTs consist of 13 protofilaments (PFs), on average, where each PF is made of a linear stack of αβ-tubulin dimers (i.e., tubulin oligomers). We begin with a series of experiments which demonstrate the flexibility of PFs toward shape changes in response to local environmental cues. First, studies show that MT-associated protein (MAP) Tau controls the diameter of microtubules upon binding to the outer surface, implying a shape change in the cross-sectional area of PFs forming the MT perimeter. The diameter of a MT may also be controlled by the charge density of a lipid bilayer membrane that coats the outer surface. We further describe an experimental study where it is unexpectedly found that the biologically relevant polyamine spermine (+4e) is able to depolymerize taxol-stabilized microtubules with efficiency that increases with decreasing temperature. This MT destabilization drives a dynamical structural transition where inside-out curving of PFs, during the depolymerization peeling process, is followed by reassembly of ring-like curved PF building blocks into an array of helical inverted tubulin tubules. We finally turn to a very recent study on pressure−distance measurements in bundles of MTs employing the small-angle X-ray scattering (SAXS)-osmotic pressure technique, which complements the surface-forces-apparatus technique developed by Jacob N. Israelachvili. These latter studies are among the very few which are beginning to shed light on the precise nature of the interactions between MTs mediated by MAP Tau in 37 °C reaction mixtures containing GTP and lacking taxol.

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“…It is widely believed that the majority of tau localizes in the axon, while the minority of tau is found in the soma and dendrites (Black et al, 1996 ; Mandell and Banker, 1996 ). For a long time, the role of tau is restricted to the establishment of neuronal polarity, axonal elongation, and transportation by its microtubule-associated ability (Caceres and Kosik, 1990 ; Esmaeli-Azad et al, 1994 ; Dixit et al, 2008 ). Evidence supports that tau is also located in dendrites and synapses of healthy neurons.…”

Section: Introductionmentioning

confidence: 99%

Tau Acts in Concert With Kinase/Phosphatase Underlying Synaptic Dysfunction

Fan

Xia

Zhou

et al. 2022

Front. Aging Neurosci.

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Alzheimer's disease (AD) is characterized by two pathological features: neurofibrillary tangles (NFTs), formed by microtubule-associated protein tau, and abnormal accumulation of amyloid-β (Aβ). Multiple evidence placed synaptic tau as the vital fact of AD pathology, especially at the very early stage of AD. In the present review, we discuss tau phosphorylation, which is critical for the dendritic localization of tau and synaptic plasticity. We review the related kinases and phosphatases implicated in the synaptic function of tau. We also review the synergistic effects of these kinases and phosphatases on tau-associated synaptic deficits. We aim to open a new perspective on the treatment of AD.

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Sense and antisense transfection analysis of tau function: tau influences net microtubule assembly, neurite outgrowth and neuritic stability

Cited by 163 publications

References 60 publications

Kinetic Stabilization of Microtubule Dynamics at Steady State by Tau and Microtubule-Binding Domains of Tau

Kinetic Stabilization of Microtubule Dynamics at Steady State by Tau and Microtubule-Binding Domains of Tau

Minireview - Microtubules and Tubulin Oligomers: Shape Transitions and Assembly by Intrinsically Disordered Protein Tau and Cationic Biomolecules

Tau Acts in Concert With Kinase/Phosphatase Underlying Synaptic Dysfunction

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