Organization of the Reserve Pool of Synaptic Vesicles in Nerve Terminals Lacking Protein Liquid Phase Components
- Authors: Nifantova N.V.1, Shishkov A.G.1, Korenkova O.M.1, Sopova E.1,2, Brodin L.2, Shupliakov O.1,2
-
Affiliations:
- Institute of Translational Biomedicine, St. Petersburg State University
- Karolinska Institutet
- Issue: Vol 41, No 2 (2024)
- Pages: 168-172
- Section: КРАТКИЕ СООБЩЕНИЯ
- URL: https://journals.rcsi.science/0233-4755/article/view/257177
- DOI: https://doi.org/10.31857/S0233475524020087
- EDN: https://elibrary.ru/xkdssv
- ID: 257177
Cite item
Open Access
Access granted
Abstract
Protein endophilin A regulates the synaptic vesicle cycle during exo- and endocytosis, and it is present in the reserve pool of synaptic vesicles (SVs), where its function is unknown. In vitro experiments suggest that endophilin via its SH3 domain interactions incorporates several components into the protein liquid phase that organizes SVs in the reserve pool. We investigated the effect of deletion of the genes encoding endophilin and one of its binding partners, dynamin, on the organization of SVs in living synapses formed by cortical neurons in culture. Experiments showed that deletion of endophilin genes does not change the density of SVs in the reserve pool. At the same time, deletion of the major dynamins 1 and 3 leads to a significant increase in the vesicle density. These results suggest that other SH3-domain-containing proteins, which are components of the protein liquid phase, complement the function of endophilin in the SV reserve pool.
Full Text
About the authors
N. V. Nifantova
Institute of Translational Biomedicine, St. Petersburg State University
Author for correspondence.
Email: oleg.shupliakov@ki.se
Russian Federation, St. Petersburg, 199034
A. G. Shishkov
Institute of Translational Biomedicine, St. Petersburg State University
Email: oleg.shupliakov@ki.se
Russian Federation, St. Petersburg, 199034
O. M. Korenkova
Institute of Translational Biomedicine, St. Petersburg State University
Email: oleg.shupliakov@ki.se
Russian Federation, St. Petersburg, 199034
E. Sopova
Institute of Translational Biomedicine, St. Petersburg State University; Karolinska Institutet
Email: oleg.shupliakov@ki.se
Russian Federation, St. Petersburg, 199034; Stockholm, 17177, Sweden
L. Brodin
Karolinska Institutet
Email: oleg.shupliakov@ki.se
Sweden, Stockholm, 17177
O. Shupliakov
Institute of Translational Biomedicine, St. Petersburg State University; Karolinska Institutet
Email: oleg.shupliakov@ki.se
Russian Federation, St. Petersburg, 199034; Stockholm, 17177, Sweden
References
- Pieribone V.A., Shupliakov O., Brodin, L., Hilfiker-Rothenfluh S., Czernik A.J., Greengard P. 1995. Distinct pools of synaptic vesicles in neurotransmitter release. Nature, 375, 493–497.
- Rizzoli S.O., Betz W.J. 2004. The structural organization of the readily releasable pool of synaptic vesicles. Science, 303, 2037–2039.
- Brodin L., Milovanovic D., Rizzoli S.O., Shupliakov O. 2022. alpha-Synuclein in the synaptic vesicle liquid phase: Active player or passive bystander? Front. Mol. Biosci., 9, 891508.
- Milovanovic D., Wu Y., Bian X., De Camilli P. 2018. A liquid phase of synapsin and lipid vesicles. Science, 361, 604–607.
- Pechstein A., Tomilin N., Fredrich K., Vorontsova O., Sopova E., Evergren E., Haucke V., Brodin L., Shupliakov O. 2020. Vesicle clustering in a living synapse depends on a synapsin region that mediates phase separation. Cell Rep., 30, 2594–2602.e3.
- Shupliakov O. 2009. The synaptic vesicle cluster: a source of endocytic proteins during neurotransmitter release. Neuroscience, 158, 204–210.
- Denker A., Kröhnert K., Bückers J., Neher E., Rizzoli S.O. 2011. The reserve pool of synaptic vesicles acts as a buffer for proteins involved in synaptic vesicle recycling. Proc. Natl. Acad. Sci. USA, 108, 17183–17188.
- Sundborger A., Soderblom C., Vorontsova O., Evergren E., Hinshaw J.E., Shupliakov O. 2011. An endophilin-dynamin complex promotes budding of clathrin-coated vesicles during synaptic vesicle recycling. J. Cell. Sci., 124, 133–143.
- Yoshida T., Takenaka K.I., Sakamoto H., Kojima Y., Sakano T., Shibayama K., Nakamura K., Hanawa-Suetsugu K., Mori Y., Hirabayashi Y., Hirose K., Takamori S. 2023. Compartmentalization of soluble endocytic proteins in synaptic vesicle clusters by phase separation. iScience, 26, 106826.
- Milosevic I., Giovedi S., Lou X., Raimondi A., Collesi C., Shen H., Paradise S., O’Toole E., Ferguson S., Cremona O., De Camilli P. 2011. Recruitment of endophilin to clathrin-coated pit necks is required for efficient vesicle uncoating after fission. Neuron, 72, 587–601.
- Raimondi A., Ferguson S.M., Lou X., Armbruster M., Paradise S., Giovedi S., Messa M., Kono N., Takasaki J., Cappello V., O’Toole E., Ryan T.A., De Camilli P. 2011. Overlapping role of dynamin isoforms in synaptic vesicle endocytosis. Neuron, 70, 1100–1114.
- Gad H., Ringstad N., Low P., Kjaerulff O., Gustafsson J., Wenk M., Di Paolo G., Nemoto Y., Crun J., Ellisman M.H., De Camilli P., Shupliakov O., Brodin L. 2000. Fission and uncoating of synaptic clathrin-coated vesicles are perturbed by disruption of interactions with the SH3 domain of endophilin. Neuron, 27, 301–312.
- Шишков А.Г., Нифантова Н.В., Коренькова О.М., Сопова Е.С., Бродин Л., Шупляков О.В. 2023. BAR-домен-содержащие белки как возможные регуляторы белковой жидкой фазы в нервных окончаниях в центральной нервной системе. Биол. мембраны, 40 (3), 155–171.
- Shishkov A.G., Nifantova N.V., Korenkova O.M., Sopova E.S., Brodin L., Shupliakov O. 2023. BAR domain proteins as putative regulators of the protein liquid phase in nerve terminals in the central nervous system. Biochemistry (Moscow) Supplement Series A: Membrane and Cell Biology, 17, 69–82.
- Ferguson S.M., Brasnjo G., Hayashi M., Wolfel M., Collesi C., Giovedi S., Raimondi A., Gong L.W., Ariel P., Paradise S., O’Toole E., Flavell R., Cremona O., Miesenbock G., Ryan T.A., De Camilli P. 2007. A selective activity-dependent requirement for dynamin 1 in synaptic vesicle endocytosis. Science, 316, 570–574.
- Hoffmann C., Sansevrino R., Morabito G., Logan C., Vabulas R.M., Ulusoy A., Ganzella M., Milovanovic D. 2021. Synapsin condensates recruit alpha-synuclein. J. Mol. Biol., 433, 166961.
- Vargas K.J., Schrod N., Davis T., Fernandez-Busnadiego R., Taguchi Y.V., Laugks U., Lucic V., Chandra S.S. 2017. synucleins have multiple effects on presynaptic architecture. Cell Rep., 18, 161–173.
Supplementary files
