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bioRxiv · 10.1101/2023.05.31.542915

TPPP Forms Liquid Condensates and Aggregates in Multiple System Atrophy

Kemal, S.·Richardson, H. S.·McAlear, T. S.·Kopach, A.·Nowacki, J. C.·Li, Y.·Bechstedt, S.·Fu, M.-m.
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Abstract

Oligodendrocytes have elaborate arbors of microtubules that extend toward axons and spiral around myelin sheaths. Oligodendrocytes rely on satellite organelles called Golgi outposts to nucleate new microtubules at sites far from the cell body. We now show that the Golgi outpost marker TPPP (tubulin polymerization promoting protein) forms liquid condensates that co-partition with tubulin in order to nucleate microtubules. In oligodendrocytes, TPPP forms either dynamic puncta or aberrant microtubule-associated aggregates. In Multiple System Atrophy (MSA), a sequela of histological events initiates with TPPP aggregation in myelin sheaths and terminates in perinuclear TPPP co-aggregation with alpha-synuclein (aSyn). Finally, recombinant TPPP aggregates are toxic to primary oligodendrocytes. Thus, while the liquid condensate property of TPPP facilitates microtubule nucleation, it also predisposes TPPP to aggregate in disease.

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Kemal, S., Richardson, H. S., McAlear, T. S., Kopach, A., Nowacki, J. C., Li, Y., Bechstedt, S., Fu, M.-m.. 2023-06-03. TPPP Forms Liquid Condensates and Aggregates in Multiple System Atrophy. https://doi.org/10.1101/2023.05.31.542915

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