June 17, 2023|,

Preprint Highlight: TPPP Forms Liquid Condensates and Aggregates in Multiple System Atrophy

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Highlighted By: Luis Bonet-Ponce, NIH

Preprint DOI: https://doi.org/10.1101/2023.05.31.542915
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Significance Statement:

  • Oligodendrocytes extend the plasma membrane surrounding axons with myelin sheaths. To accomplish this, oligodendrocytes rely on Golgi outposts, a compartment able to nucleate new microtubules in distal regions of the cell. However, how oligodendrocyte microtubule nucleation might contribute to neurodegeneration remains unclear.
  • The authors study tubulin polymerization promoting protein (TPPP), a protein previously shown to promote microtubule nucleation from Golgi outposts. They show that in order to nucleate microtubules, TPPP forms liquid condensates, a property that enables its aggregation. TPPP aggregates are found in oligodendrocytes in the brains of multiple system atrophy patients. Remarkably, these aggregates colocalize with the Lewy-body marker α-synuclein, as observed by confocal microscopy and immunoblotting.
  • This work proposes a role for TPPP in neurodegeneration through its liquid condensation and toxic pro-aggregation properties.

Read the Preprint:

Shahrnaz Kemal, Hunter S. Richardson, Thomas S. McAlear, Andrii Kopach, Joseph C. Nowacki, Yan Li, Susanne Bechstedt, Meng-meng Fu (2023). TPPP Forms Liquid Condensates and Aggregates in Multiple System Atrophy. bioRxiv; doi: https://doi.org/10.1101/2023.05.31.542915

 

 

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