Actin dynamics provides membrane tension to merge fusing vesicles into the plasma membrane

Peter J. Wen; Staffan Grenklo; Gianvito Arpino; Xinyu Tan; Hsien Shun Liao; Johanna Heureaux; Shi Yong Peng; Hsueh Cheng Chiang; Edaeni Hamid; Wei Dong Zhao; Wonchul Shin; Tuomas Näreoja; Emma Evergren; Yinghui Jin; Roger Karlsson; Steven N. Ebert; Albert Jin; Allen P. Liu; Oleg Shupliakov; Ling Gang Wu

doi:10.1038/ncomms12604

Actin dynamics provides membrane tension to merge fusing vesicles into the plasma membrane

Peter J. Wen, Staffan Grenklo, Gianvito Arpino, Xinyu Tan, Hsien Shun Liao, Johanna Heureaux, Shi Yong Peng, Hsueh Cheng Chiang, Edaeni Hamid, Wei Dong Zhao, Wonchul Shin, Tuomas Näreoja, Emma Evergren, Yinghui Jin, Roger Karlsson, Steven N. Ebert, Albert Jin, Allen P. Liu, Oleg Shupliakov, Ling Gang Wu

Department of Pharmacology

Research output: Contribution to journal › Article › peer-review

63 Citations (Scopus)

Abstract

Vesicle fusion is executed via formation of an Ω-shaped structure (Ω-profile), followed by closure (kiss-and-run) or merging of the Ω-profile into the plasma membrane (full fusion). Although Ω-profile closure limits release but recycles vesicles economically, Ω-profile merging facilitates release but couples to classical endocytosis for recycling. Despite its crucial role in determining exocytosis/endocytosis modes, how Ω-profile merging is mediated is poorly understood in endocrine cells and neurons containing small ∼30-300 nm vesicles. Here, using confocal and super-resolution STED imaging, force measurements, pharmacology and gene knockout, we show that dynamic assembly of filamentous actin, involving ATP hydrolysis, N-WASP and formin, mediates Ω-profile merging by providing sufficient plasma membrane tension to shrink the Ω-profile in neuroendocrine chromaffin cells containing ∼300 nm vesicles. Actin-directed compounds also induce Ω-profile accumulation at lamprey synaptic active zones, suggesting that actin may mediate Ω-profile merging at synapses. These results uncover molecular and biophysical mechanisms underlying Ω-profile merging.

Original language	English
Article number	12604
Journal	Nature communications
Volume	7
DOIs	https://doi.org/10.1038/ncomms12604
Publication status	Published - 2016 Aug 31

All Science Journal Classification (ASJC) codes

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)

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Wen, P. J., Grenklo, S., Arpino, G., Tan, X., Liao, H. S., Heureaux, J., Peng, S. Y., Chiang, H. C., Hamid, E., Zhao, W. D., Shin, W., Näreoja, T., Evergren, E., Jin, Y., Karlsson, R., Ebert, S. N., Jin, A., Liu, A. P., Shupliakov, O., & Wu, L. G. (2016). Actin dynamics provides membrane tension to merge fusing vesicles into the plasma membrane. Nature communications, 7, [12604]. https://doi.org/10.1038/ncomms12604

Wen, Peter J. ; Grenklo, Staffan ; Arpino, Gianvito ; Tan, Xinyu ; Liao, Hsien Shun ; Heureaux, Johanna ; Peng, Shi Yong ; Chiang, Hsueh Cheng ; Hamid, Edaeni ; Zhao, Wei Dong ; Shin, Wonchul ; Näreoja, Tuomas ; Evergren, Emma ; Jin, Yinghui ; Karlsson, Roger ; Ebert, Steven N. ; Jin, Albert ; Liu, Allen P. ; Shupliakov, Oleg ; Wu, Ling Gang. / Actin dynamics provides membrane tension to merge fusing vesicles into the plasma membrane. In: Nature communications. 2016 ; Vol. 7.

@article{bf86dc62476a4f908f80265ebeab18a6,

title = "Actin dynamics provides membrane tension to merge fusing vesicles into the plasma membrane",

abstract = "Vesicle fusion is executed via formation of an Ω-shaped structure (Ω-profile), followed by closure (kiss-and-run) or merging of the Ω-profile into the plasma membrane (full fusion). Although Ω-profile closure limits release but recycles vesicles economically, Ω-profile merging facilitates release but couples to classical endocytosis for recycling. Despite its crucial role in determining exocytosis/endocytosis modes, how Ω-profile merging is mediated is poorly understood in endocrine cells and neurons containing small ∼30-300 nm vesicles. Here, using confocal and super-resolution STED imaging, force measurements, pharmacology and gene knockout, we show that dynamic assembly of filamentous actin, involving ATP hydrolysis, N-WASP and formin, mediates Ω-profile merging by providing sufficient plasma membrane tension to shrink the Ω-profile in neuroendocrine chromaffin cells containing ∼300 nm vesicles. Actin-directed compounds also induce Ω-profile accumulation at lamprey synaptic active zones, suggesting that actin may mediate Ω-profile merging at synapses. These results uncover molecular and biophysical mechanisms underlying Ω-profile merging.",

author = "Wen, {Peter J.} and Staffan Grenklo and Gianvito Arpino and Xinyu Tan and Liao, {Hsien Shun} and Johanna Heureaux and Peng, {Shi Yong} and Chiang, {Hsueh Cheng} and Edaeni Hamid and Zhao, {Wei Dong} and Wonchul Shin and Tuomas N{\"a}reoja and Emma Evergren and Yinghui Jin and Roger Karlsson and Ebert, {Steven N.} and Albert Jin and Liu, {Allen P.} and Oleg Shupliakov and Wu, {Ling Gang}",

note = "Funding Information: We thank Dr James Ervasti for providing Actbloxp mice. This work was supported by the National Institute of Neurological Disorders and Stroke Intramural Research Program (ZIA NS003009-13 and ZIA NS003105-08) to L.G.W. and by grants from the Swedish Research Council (project 13473), Parkinsonfonden, Hj?rnfonden and the Russian Science Foundation (project number 16-15-10273) to O.S.",

year = "2016",

month = aug,

day = "31",

doi = "10.1038/ncomms12604",

language = "English",

volume = "7",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

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Wen, PJ, Grenklo, S, Arpino, G, Tan, X, Liao, HS, Heureaux, J, Peng, SY, Chiang, HC, Hamid, E, Zhao, WD, Shin, W, Näreoja, T, Evergren, E, Jin, Y, Karlsson, R, Ebert, SN, Jin, A, Liu, AP, Shupliakov, O & Wu, LG 2016, 'Actin dynamics provides membrane tension to merge fusing vesicles into the plasma membrane', Nature communications, vol. 7, 12604. https://doi.org/10.1038/ncomms12604

Actin dynamics provides membrane tension to merge fusing vesicles into the plasma membrane. / Wen, Peter J.; Grenklo, Staffan; Arpino, Gianvito; Tan, Xinyu; Liao, Hsien Shun; Heureaux, Johanna; Peng, Shi Yong; Chiang, Hsueh Cheng; Hamid, Edaeni; Zhao, Wei Dong; Shin, Wonchul; Näreoja, Tuomas; Evergren, Emma; Jin, Yinghui; Karlsson, Roger; Ebert, Steven N.; Jin, Albert; Liu, Allen P.; Shupliakov, Oleg; Wu, Ling Gang.

In: Nature communications, Vol. 7, 12604, 31.08.2016.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Actin dynamics provides membrane tension to merge fusing vesicles into the plasma membrane

AU - Wen, Peter J.

AU - Grenklo, Staffan

AU - Arpino, Gianvito

AU - Tan, Xinyu

AU - Liao, Hsien Shun

AU - Heureaux, Johanna

AU - Peng, Shi Yong

AU - Chiang, Hsueh Cheng

AU - Hamid, Edaeni

AU - Zhao, Wei Dong

AU - Shin, Wonchul

AU - Näreoja, Tuomas

AU - Evergren, Emma

AU - Jin, Yinghui

AU - Karlsson, Roger

AU - Ebert, Steven N.

AU - Jin, Albert

AU - Liu, Allen P.

AU - Shupliakov, Oleg

AU - Wu, Ling Gang

N1 - Funding Information: We thank Dr James Ervasti for providing Actbloxp mice. This work was supported by the National Institute of Neurological Disorders and Stroke Intramural Research Program (ZIA NS003009-13 and ZIA NS003105-08) to L.G.W. and by grants from the Swedish Research Council (project 13473), Parkinsonfonden, Hj?rnfonden and the Russian Science Foundation (project number 16-15-10273) to O.S.

PY - 2016/8/31

Y1 - 2016/8/31

N2 - Vesicle fusion is executed via formation of an Ω-shaped structure (Ω-profile), followed by closure (kiss-and-run) or merging of the Ω-profile into the plasma membrane (full fusion). Although Ω-profile closure limits release but recycles vesicles economically, Ω-profile merging facilitates release but couples to classical endocytosis for recycling. Despite its crucial role in determining exocytosis/endocytosis modes, how Ω-profile merging is mediated is poorly understood in endocrine cells and neurons containing small ∼30-300 nm vesicles. Here, using confocal and super-resolution STED imaging, force measurements, pharmacology and gene knockout, we show that dynamic assembly of filamentous actin, involving ATP hydrolysis, N-WASP and formin, mediates Ω-profile merging by providing sufficient plasma membrane tension to shrink the Ω-profile in neuroendocrine chromaffin cells containing ∼300 nm vesicles. Actin-directed compounds also induce Ω-profile accumulation at lamprey synaptic active zones, suggesting that actin may mediate Ω-profile merging at synapses. These results uncover molecular and biophysical mechanisms underlying Ω-profile merging.

AB - Vesicle fusion is executed via formation of an Ω-shaped structure (Ω-profile), followed by closure (kiss-and-run) or merging of the Ω-profile into the plasma membrane (full fusion). Although Ω-profile closure limits release but recycles vesicles economically, Ω-profile merging facilitates release but couples to classical endocytosis for recycling. Despite its crucial role in determining exocytosis/endocytosis modes, how Ω-profile merging is mediated is poorly understood in endocrine cells and neurons containing small ∼30-300 nm vesicles. Here, using confocal and super-resolution STED imaging, force measurements, pharmacology and gene knockout, we show that dynamic assembly of filamentous actin, involving ATP hydrolysis, N-WASP and formin, mediates Ω-profile merging by providing sufficient plasma membrane tension to shrink the Ω-profile in neuroendocrine chromaffin cells containing ∼300 nm vesicles. Actin-directed compounds also induce Ω-profile accumulation at lamprey synaptic active zones, suggesting that actin may mediate Ω-profile merging at synapses. These results uncover molecular and biophysical mechanisms underlying Ω-profile merging.

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