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Phase Diagram Characterization Using Magnetic Beads as Liquid Carriers
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EFhd2 Affects Tau Liquid-Liquid Phase Separation.

Irving E Vega1,2,3, Andrew Umstead1, Nicholas M Kanaan1,2,4

  • 1Department of Translational Science and Molecular Medicine, College of Human Medicine, Grand Rapids, MI, United States.

Frontiers in Neuroscience
|August 29, 2019
PubMed
Summary
This summary is machine-generated.

EFhd2 protein influences tau protein liquid-liquid phase separation. This interaction, dependent on calcium and EFhd2

Keywords:
Alzheimer’s diseaseEFhd2liquid–liquid phase separationneurodegenerationtautauopathy

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Area of Science:

  • Neuroscience
  • Biochemistry
  • Molecular Biology

Background:

  • The pathological transformation of tau proteins in Alzheimer's disease (AD) and related dementias is poorly understood.
  • Identifying factors that modulate toxic tau oligomer formation is crucial for developing therapeutic strategies.
  • EFhd2 protein has been previously linked to aggregated tau species in AD brains.

Purpose of the Study:

  • To investigate the role of EFhd2 in modulating tau protein liquid-liquid phase separation (LLPS).
  • To characterize the influence of calcium and EFhd2's coiled-coil domain on tau LLPS.
  • To understand how EFhd2 affects the structural dynamics of tau proteins.

Main Methods:

  • In vitro experiments examining tau protein behavior under molecular crowding conditions.
  • Co-incubation of EFhd2 and tau proteins with and without calcium.
  • Assessment of protein aggregation and phase separation properties.

Main Results:

  • EFhd2 alters tau liquid phase behavior in a calcium-dependent manner.
  • In the absence of calcium, EFhd2 and tau form solid-like aggregates.
  • In the presence of calcium, EFhd2 and tau co-phase separate into liquid droplets, requiring EFhd2's coiled-coil domain.

Conclusions:

  • EFhd2 significantly modulates tau protein liquid-liquid phase separation in vitro.
  • The interaction between EFhd2 and tau is dependent on calcium and EFhd2's coiled-coil domain.
  • EFhd2 influences the structural dynamics of tau, potentially impacting its pathological aggregation.