Tau forms synaptic nano-biomolecular condensates controlling the dynamic clustering of recycling synaptic vesicles.

Autor: Longfield SF; Clem Jones Centre for Ageing Dementia Research (CJCADR), Queensland Brain Institute (QBI), The University of Queensland; St Lucia Campus, Brisbane, QLD, 4072, Australia., Mollazade M; Clem Jones Centre for Ageing Dementia Research (CJCADR), Queensland Brain Institute (QBI), The University of Queensland; St Lucia Campus, Brisbane, QLD, 4072, Australia., Wallis TP; Clem Jones Centre for Ageing Dementia Research (CJCADR), Queensland Brain Institute (QBI), The University of Queensland; St Lucia Campus, Brisbane, QLD, 4072, Australia., Gormal RS; Clem Jones Centre for Ageing Dementia Research (CJCADR), Queensland Brain Institute (QBI), The University of Queensland; St Lucia Campus, Brisbane, QLD, 4072, Australia., Joensuu M; Clem Jones Centre for Ageing Dementia Research (CJCADR), Queensland Brain Institute (QBI), The University of Queensland; St Lucia Campus, Brisbane, QLD, 4072, Australia.; Australian Institute for Bioengineering and Nanotechnology, The University of Queensland; St Lucia Campus, Brisbane, QLD, 4072, Australia., Wark JR; Synapse Proteomics, Children's Medical Research Institute (CMRI), The University of Sydney, 214 Hawkesbury Road, Westmead, NSW, 2145, Australia., van Waardenberg AJ; i-Synapse, Cairns, QLD, 4870, Australia., Small C; Clem Jones Centre for Ageing Dementia Research (CJCADR), Queensland Brain Institute (QBI), The University of Queensland; St Lucia Campus, Brisbane, QLD, 4072, Australia., Graham ME; Synapse Proteomics, Children's Medical Research Institute (CMRI), The University of Sydney, 214 Hawkesbury Road, Westmead, NSW, 2145, Australia., Meunier FA; Clem Jones Centre for Ageing Dementia Research (CJCADR), Queensland Brain Institute (QBI), The University of Queensland; St Lucia Campus, Brisbane, QLD, 4072, Australia. f.meunier@uq.edu.au.; School of Biomedical Science, The University of Queensland; St Lucia Campus, Brisbane, QLD, 4072, Australia. f.meunier@uq.edu.au., Martínez-Mármol R; Clem Jones Centre for Ageing Dementia Research (CJCADR), Queensland Brain Institute (QBI), The University of Queensland; St Lucia Campus, Brisbane, QLD, 4072, Australia. r.martinezmarmol@uq.edu.au.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Nov 10; Vol. 14 (1), pp. 7277. Date of Electronic Publication: 2023 Nov 10.
DOI: 10.1038/s41467-023-43130-4
Abstrakt: Neuronal communication relies on the release of neurotransmitters from various populations of synaptic vesicles. Despite displaying vastly different release probabilities and mobilities, the reserve and recycling pool of vesicles co-exist within a single cluster suggesting that small synaptic biomolecular condensates could regulate their nanoscale distribution. Here, we performed a large-scale activity-dependent phosphoproteome analysis of hippocampal neurons in vitro and identified Tau as a highly phosphorylated and disordered candidate protein. Single-molecule super-resolution microscopy revealed that Tau undergoes liquid-liquid phase separation to generate presynaptic nanoclusters whose density and number are regulated by activity. This activity-dependent diffusion process allows Tau to translocate into the presynapse where it forms biomolecular condensates, to selectively control the mobility of recycling vesicles. Tau, therefore, forms presynaptic nano-biomolecular condensates that regulate the nanoscale organization of synaptic vesicles in an activity-dependent manner.
(© 2023. The Author(s).)
Databáze: MEDLINE
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