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Tau mediates microtubule bundle architectures mimicking fascicles of microtubules found in the axon initial segment
by
Wilson, Leslie
, Feinstein, Stuart C.
, Miller, Herbert P.
, Safinya, Cyrus R.
, Deek, Joanna
, Chung, Peter J.
, Song, Chaeyeon
, Choi, Myung Chul
, Li, Youli
in
631/378/340
/ 631/57/2272
/ 631/80/128/1653
/ 82
/ 82/80
/ 82/83
/ Animals
/ Axon Initial Segment - metabolism
/ Axon Initial Segment - ultrastructure
/ BASIC BIOLOGICAL SCIENCES
/ Cattle
/ Developmental biology
/ Humanities and Social Sciences
/ Microscopy
/ Microtubules - metabolism
/ Microtubules - ultrastructure
/ multidisciplinary
/ Osmotic Pressure
/ Protein Domains
/ Scattering, Small Angle
/ Science
/ Science (multidisciplinary)
/ tau Proteins - chemistry
/ tau Proteins - metabolism
/ Thermodynamics
/ X-Ray Diffraction
2016
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Tau mediates microtubule bundle architectures mimicking fascicles of microtubules found in the axon initial segment
by
Wilson, Leslie
, Feinstein, Stuart C.
, Miller, Herbert P.
, Safinya, Cyrus R.
, Deek, Joanna
, Chung, Peter J.
, Song, Chaeyeon
, Choi, Myung Chul
, Li, Youli
in
631/378/340
/ 631/57/2272
/ 631/80/128/1653
/ 82
/ 82/80
/ 82/83
/ Animals
/ Axon Initial Segment - metabolism
/ Axon Initial Segment - ultrastructure
/ BASIC BIOLOGICAL SCIENCES
/ Cattle
/ Developmental biology
/ Humanities and Social Sciences
/ Microscopy
/ Microtubules - metabolism
/ Microtubules - ultrastructure
/ multidisciplinary
/ Osmotic Pressure
/ Protein Domains
/ Scattering, Small Angle
/ Science
/ Science (multidisciplinary)
/ tau Proteins - chemistry
/ tau Proteins - metabolism
/ Thermodynamics
/ X-Ray Diffraction
2016
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Tau mediates microtubule bundle architectures mimicking fascicles of microtubules found in the axon initial segment
by
Wilson, Leslie
, Feinstein, Stuart C.
, Miller, Herbert P.
, Safinya, Cyrus R.
, Deek, Joanna
, Chung, Peter J.
, Song, Chaeyeon
, Choi, Myung Chul
, Li, Youli
in
631/378/340
/ 631/57/2272
/ 631/80/128/1653
/ 82
/ 82/80
/ 82/83
/ Animals
/ Axon Initial Segment - metabolism
/ Axon Initial Segment - ultrastructure
/ BASIC BIOLOGICAL SCIENCES
/ Cattle
/ Developmental biology
/ Humanities and Social Sciences
/ Microscopy
/ Microtubules - metabolism
/ Microtubules - ultrastructure
/ multidisciplinary
/ Osmotic Pressure
/ Protein Domains
/ Scattering, Small Angle
/ Science
/ Science (multidisciplinary)
/ tau Proteins - chemistry
/ tau Proteins - metabolism
/ Thermodynamics
/ X-Ray Diffraction
2016
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Tau mediates microtubule bundle architectures mimicking fascicles of microtubules found in the axon initial segment
Journal Article
Tau mediates microtubule bundle architectures mimicking fascicles of microtubules found in the axon initial segment
2016
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Overview
Tau, an intrinsically disordered protein confined to neuronal axons, binds to and regulates microtubule dynamics. Although there have been observations of string-like microtubule fascicles in the axon initial segment (AIS) and hexagonal bundles in neurite-like processes in non-neuronal cells overexpressing Tau, cell-free reconstitutions have not replicated either geometry. Here we map out the energy landscape of Tau-mediated, GTP-dependent ‘active’ microtubule bundles at 37 °C, as revealed by synchrotron SAXS and TEM. Widely spaced bundles (wall-to-wall distance
D
w–w
≈25–41 nm) with hexagonal and string-like symmetry are observed, the latter mimicking bundles found in the AIS. A second energy minimum (
D
w–w
≈16–23 nm) is revealed under osmotic pressure. The wide spacing results from a balance between repulsive forces, due to Tau’s projection domain (PD), and a stabilizing sum of transient sub-
k
B
T
cationic/anionic charge–charge attractions mediated by weakly penetrating opposing PDs. This landscape would be significantly affected by charge-altering modifications of Tau associated with neurodegeneration.
Tau, an intrinsically disordered axonal protein, binds to and regulates microtubule dynamics. Here, the authors use SAXS and electron microscopy to examine the architectures of microtubule bundles, including those mimicking microtubule fascicles in the axon initial segment.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
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