SV2A controls the surface nanoclustering and endocytic recruitment of Syt1 during synaptic vesicle recycling.

Autor: Small C; Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, the University of Queensland, Brisbane, Queensland, Australia., Harper C; Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, UK.; Muir Maxwell Epilepsy Centre, University of Edinburgh, Edinburgh, UK.; Simons Initiative for the Developing Brain, University of Edinburgh, Edinburgh, UK., Jiang A; Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, the University of Queensland, Brisbane, Queensland, Australia., Kontaxi C; Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, UK.; Muir Maxwell Epilepsy Centre, University of Edinburgh, Edinburgh, UK.; Simons Initiative for the Developing Brain, University of Edinburgh, Edinburgh, UK., Pronot M; Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, UK.; Muir Maxwell Epilepsy Centre, University of Edinburgh, Edinburgh, UK.; Simons Initiative for the Developing Brain, University of Edinburgh, Edinburgh, UK., Yak N; Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, the University of Queensland, Brisbane, Queensland, Australia., Malapaka A; Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, the University of Queensland, Brisbane, Queensland, Australia., Davenport EC; Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, UK.; Muir Maxwell Epilepsy Centre, University of Edinburgh, Edinburgh, UK.; Simons Initiative for the Developing Brain, University of Edinburgh, Edinburgh, UK., Wallis TP; Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, the University of Queensland, Brisbane, Queensland, Australia., Gormal RS; Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, the University of Queensland, Brisbane, Queensland, Australia., Joensuu M; Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, the University of Queensland, Brisbane, Queensland, Australia., Martínez-Mármol R; Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, the University of Queensland, Brisbane, Queensland, Australia., Cousin MA; Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, UK.; Muir Maxwell Epilepsy Centre, University of Edinburgh, Edinburgh, UK.; Simons Initiative for the Developing Brain, University of Edinburgh, Edinburgh, UK., Meunier FA; Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, the University of Queensland, Brisbane, Queensland, Australia.; School of Biomedical Sciences, the University of Queensland, Brisbane, Queensland, Australia.
Jazyk: angličtina
Zdroj: Journal of neurochemistry [J Neurochem] 2024 Aug 01. Date of Electronic Publication: 2024 Aug 01.
DOI: 10.1111/jnc.16186
Abstrakt: Following exocytosis, the recapture of plasma membrane-stranded vesicular proteins into recycling synaptic vesicles (SVs) is essential for sustaining neurotransmission. Surface clustering of vesicular proteins has been proposed to act as a 'pre-assembly' mechanism for endocytosis that ensures high-fidelity retrieval of SV cargo. Here, we used single-molecule imaging to examine the nanoclustering of synaptotagmin-1 (Syt1) and synaptic vesicle protein 2A (SV2A) in hippocampal neurons. Syt1 forms surface nanoclusters through the interaction of its C2B domain with SV2A, which are sensitive to mutations in this domain (Syt1 K326A/K328A ) and SV2A knockdown. SV2A co-clustering with Syt1 is reduced by blocking SV2A's cognate interaction with Syt1 (SV2A T84A ). Surprisingly, impairing SV2A-Syt1 nanoclustering enhanced the plasma membrane recruitment of key endocytic protein dynamin-1, causing accelerated Syt1 endocytosis, altered intracellular sorting and decreased trafficking of Syt1 to Rab5-positive endocytic compartments. Therefore, SV2A and Syt1 are segregated from the endocytic machinery in surface nanoclusters, limiting dynamin recruitment and negatively regulating Syt1 entry into recycling SVs.
(© 2024 The Author(s). Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.)
Databáze: MEDLINE
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