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@ARTICLE{Rai:155725,
author = {Rai, Sandeep K and Savastano, Adriana and Singh, Priyanka
and Mukhopadhyay, Samrat and Zweckstetter, Markus},
title = {{L}iquid-liquid phase separation of tau: {F}rom molecular
biophysics to physiology and disease.},
journal = {Protein science},
volume = {30},
number = {7},
issn = {1469-896X},
address = {Bethesda, Md.},
publisher = {Protein Society},
reportid = {DZNE-2021-00893},
pages = {1294 - 1314},
year = {2021},
abstract = {Biomolecular condensation via liquid-liquid phase
separation (LLPS) of intrinsically disordered
proteins/regions (IDPs/IDRs), with and without nucleic
acids, has drawn widespread interest due to the rapidly
unfolding role of phase-separated condensates in a diverse
range of cellular functions and human diseases. Biomolecular
condensates form via transient and multivalent
intermolecular forces that sequester proteins and nucleic
acids into liquid-like membrane-less compartments. However,
aberrant phase transitions into gel-like or solid-like
aggregates might play an important role in neurodegenerative
and other diseases. Tau, a microtubule-associated neuronal
IDP, is involved in microtubule stabilization, regulates
axonal outgrowth and transport in neurons. A growing body of
evidence indicates that tau can accomplish some of its
cellular activities via LLPS. However, liquid-to-solid
transition resulting in the abnormal aggregation of tau is
associated with neurodegenerative diseases. The physical
chemistry of tau is crucial for governing its propensity for
biomolecular condensation which is governed by various
intermolecular and intramolecular interactions leading to
simple one-component and complex multi-component
condensates. In this review, we aim at capturing the current
scientific state in unveiling the intriguing molecular
mechanism of phase separation of tau. We particularly focus
on the amalgamation of existing and emerging biophysical
tools that offer unique spatiotemporal resolutions on a wide
range of length- and time-scales. We also discuss the link
between quantitative biophysical measurements and novel
biological insights into biomolecular condensation of tau.
We believe that this account will provide a broad and
multidisciplinary view of phase separation of tau and its
association with physiology and disease.},
subtyp = {Review Article},
keywords = {Biomolecular Condensates: chemistry / Humans /
Intrinsically Disordered Proteins: chemistry / Intrinsically
Disordered Proteins: isolation $\&$ purification /
Intrinsically Disordered Proteins: metabolism /
Neurodegenerative Diseases: metabolism / tau Proteins:
chemistry / tau Proteins: isolation $\&$ purification / tau
Proteins: metabolism},
cin = {AG Zweckstetter},
ddc = {610},
cid = {I:(DE-2719)1410001},
pnm = {352 - Disease Mechanisms (POF4-352)},
pid = {G:(DE-HGF)POF4-352},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:33930220},
pmc = {pmc:PMC8197432},
doi = {10.1002/pro.4093},
url = {https://pub.dzne.de/record/155725},
}