Compartmentalization of soluble endocytic proteins in synaptic vesicle clusters by phase separation
Summary: Synaptic vesicle (SV) clusters, which reportedly result from synapsin’s capacity to undergo liquid-liquid phase separation (LLPS), constitute the structural basis for neurotransmission. Although these clusters contain various endocytic accessory proteins, how endocytic proteins accumulate i...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-06-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223009033 |
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| author | Tomofumi Yoshida Koh-ichiro Takenaka Hirokazu Sakamoto Yusuke Kojima Takumi Sakano Koyo Shibayama Koki Nakamura Kyoko Hanawa-Suetsugu Yasunori Mori Yusuke Hirabayashi Kenzo Hirose Shigeo Takamori |
| author_facet | Tomofumi Yoshida Koh-ichiro Takenaka Hirokazu Sakamoto Yusuke Kojima Takumi Sakano Koyo Shibayama Koki Nakamura Kyoko Hanawa-Suetsugu Yasunori Mori Yusuke Hirabayashi Kenzo Hirose Shigeo Takamori |
| author_sort | Tomofumi Yoshida |
| collection | DOAJ |
| description | Summary: Synaptic vesicle (SV) clusters, which reportedly result from synapsin’s capacity to undergo liquid-liquid phase separation (LLPS), constitute the structural basis for neurotransmission. Although these clusters contain various endocytic accessory proteins, how endocytic proteins accumulate in SV clusters remains unknown. Here, we report that endophilin A1 (EndoA1), the endocytic scaffold protein, undergoes LLPS under physiologically relevant concentrations at presynaptic terminals. On heterologous expression, EndoA1 facilitates the formation of synapsin condensates and accumulates in SV-like vesicle clusters via synapsin. Moreover, EndoA1 condensates recruit endocytic proteins such as dynamin 1, amphiphysin, and intersectin 1, none of which are recruited in vesicle clusters by synapsin. In cultured neurons, like synapsin, EndoA1 is compartmentalized in SV clusters through LLPS, exhibiting activity-dependent dispersion/reassembly cycles. Thus, beyond its essential function in SV endocytosis, EndoA1 serves an additional structural function by undergoing LLPS, thereby accumulating various endocytic proteins in dynamic SV clusters in concert with synapsin. |
| first_indexed | 2024-03-13T10:28:07Z |
| format | Article |
| id | doaj.art-9cb38b29693e4b48be9ad754c78ae8d1 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-13T10:28:07Z |
| publishDate | 2023-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-9cb38b29693e4b48be9ad754c78ae8d12023-05-19T04:46:19ZengElsevieriScience2589-00422023-06-01266106826Compartmentalization of soluble endocytic proteins in synaptic vesicle clusters by phase separationTomofumi Yoshida0Koh-ichiro Takenaka1Hirokazu Sakamoto2Yusuke Kojima3Takumi Sakano4Koyo Shibayama5Koki Nakamura6Kyoko Hanawa-Suetsugu7Yasunori Mori8Yusuke Hirabayashi9Kenzo Hirose10Shigeo Takamori11Laboratory of Neural Membrane Biology, Graduate School of Brain Science, Doshisha University, Kyoto 610-0394, JapanLaboratory of Neural Membrane Biology, Graduate School of Brain Science, Doshisha University, Kyoto 610-0394, JapanDepartment of Pharmacology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, JapanDepartment of Pharmacology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, JapanDepartment of Chemistry and Biotechnology, School of Engineering, The University of Tokyo, Tokyo 113-0033, JapanDepartment of Chemistry and Biotechnology, School of Engineering, The University of Tokyo, Tokyo 113-0033, JapanDepartment of Chemistry and Biotechnology, School of Engineering, The University of Tokyo, Tokyo 113-0033, JapanLaboratory of Neural Membrane Biology, Graduate School of Brain Science, Doshisha University, Kyoto 610-0394, JapanLaboratory of Neural Membrane Biology, Graduate School of Brain Science, Doshisha University, Kyoto 610-0394, JapanDepartment of Chemistry and Biotechnology, School of Engineering, The University of Tokyo, Tokyo 113-0033, JapanDepartment of Pharmacology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan; International Research Center for Neurointelligence (WPI-IRCN), The University of Tokyo, Tokyo 113-0033, JapanLaboratory of Neural Membrane Biology, Graduate School of Brain Science, Doshisha University, Kyoto 610-0394, Japan; Corresponding authorSummary: Synaptic vesicle (SV) clusters, which reportedly result from synapsin’s capacity to undergo liquid-liquid phase separation (LLPS), constitute the structural basis for neurotransmission. Although these clusters contain various endocytic accessory proteins, how endocytic proteins accumulate in SV clusters remains unknown. Here, we report that endophilin A1 (EndoA1), the endocytic scaffold protein, undergoes LLPS under physiologically relevant concentrations at presynaptic terminals. On heterologous expression, EndoA1 facilitates the formation of synapsin condensates and accumulates in SV-like vesicle clusters via synapsin. Moreover, EndoA1 condensates recruit endocytic proteins such as dynamin 1, amphiphysin, and intersectin 1, none of which are recruited in vesicle clusters by synapsin. In cultured neurons, like synapsin, EndoA1 is compartmentalized in SV clusters through LLPS, exhibiting activity-dependent dispersion/reassembly cycles. Thus, beyond its essential function in SV endocytosis, EndoA1 serves an additional structural function by undergoing LLPS, thereby accumulating various endocytic proteins in dynamic SV clusters in concert with synapsin.http://www.sciencedirect.com/science/article/pii/S2589004223009033Biological sciencesMolecular biologyCell biology |
| spellingShingle | Tomofumi Yoshida Koh-ichiro Takenaka Hirokazu Sakamoto Yusuke Kojima Takumi Sakano Koyo Shibayama Koki Nakamura Kyoko Hanawa-Suetsugu Yasunori Mori Yusuke Hirabayashi Kenzo Hirose Shigeo Takamori Compartmentalization of soluble endocytic proteins in synaptic vesicle clusters by phase separation iScience Biological sciences Molecular biology Cell biology |
| title | Compartmentalization of soluble endocytic proteins in synaptic vesicle clusters by phase separation |
| title_full | Compartmentalization of soluble endocytic proteins in synaptic vesicle clusters by phase separation |
| title_fullStr | Compartmentalization of soluble endocytic proteins in synaptic vesicle clusters by phase separation |
| title_full_unstemmed | Compartmentalization of soluble endocytic proteins in synaptic vesicle clusters by phase separation |
| title_short | Compartmentalization of soluble endocytic proteins in synaptic vesicle clusters by phase separation |
| title_sort | compartmentalization of soluble endocytic proteins in synaptic vesicle clusters by phase separation |
| topic | Biological sciences Molecular biology Cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223009033 |
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