Tau and α-synuclein shape microtubule organization and microtubule-dependent transport in neuronal dendrites

Rierola, M.; Trushina, N. I.; Monteiro-Abreu, N.; Conze, C.; Holtmannspoetter, M.; Kurre, R.; Holzer, M.; Arendt, T.; Heinisch, J. J.; Brandt, R.; Bakota, L.

doi:10.1101/2022.06.09.495530

bioRxiv · 10.1101/2022.06.09.495530

Tau and α-synuclein shape microtubule organization and microtubule-dependent transport in neuronal dendrites

Rierola, M.·Trushina, N. I.·Monteiro-Abreu, N.·Conze, C.·Holtmannspoetter, M.·Kurre, R.·Holzer, M.·Arendt, T.·Heinisch, J. J.·Brandt, R.·Bakota, L.

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Abstract

Tau and -synuclein are major players in neurodegenerative diseases, but their physiological role, particularly in dendrites, is poorly understood. Here we show that, surprisingly, lack of tau protein induces the development of a more elaborate dendritic arbor of hippocampal pyramidal cells in organotypic tissue. Using high-speed volumetric lattice light-sheet microscopy and single particle tracking, we found a more directional KIF1A-mediated transport in dendrites of Tau KO cells. Increased transport processivity correlated with longer and straighter dendritic microtubules as revealed by three-dimensional super-resolution microscopy of cultured hippocampal neurons. Unbiased mass spectrometric analysis of tissue showed highly increased expression of -synuclein in Tau KO hippocampi. Overexpression of -synuclein mimicked the transport characteristics observed in Tau KO cells. Our data indicate that tau and -synuclein shape microtubule-dependent transport in neuronal dendrites, thereby promoting dendritic arborization during maturation. Furthermore, the data demonstrate that transport efficiency and length and straightness of microtubules are correlated.

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Rierola, M., Trushina, N. I., Monteiro-Abreu, N., Conze, C., Holtmannspoetter, M., Kurre, R., Holzer, M., Arendt, T., Heinisch, J. J., Brandt, R., Bakota, L.. 2022-06-12. Tau and α-synuclein shape microtubule organization and microtubule-dependent transport in neuronal dendrites. https://doi.org/10.1101/2022.06.09.495530

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