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Intersectin associates with synapsin and regulates its nanoscale localization and function. / Gerth, Fabian; Jäpel, Maria; Pechstein, Arndt; Kochlamazashvili, Gaga; Lehmann, Martin; Puchkov, Dmytro; Onofri, Franco; Benfenati, Fabio; Nikonenko, Alexander G.; Fredrich, Kristin; Shupliakov, Oleg; Maritzen, Tanja; Freund, Christian; Haucke, Volker.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 114, No. 45, 07.11.2017, p. 12057-12062.

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

Harvard

Gerth, F, Jäpel, M, Pechstein, A, Kochlamazashvili, G, Lehmann, M, Puchkov, D, Onofri, F, Benfenati, F, Nikonenko, AG, Fredrich, K, Shupliakov, O, Maritzen, T, Freund, C & Haucke, V 2017, 'Intersectin associates with synapsin and regulates its nanoscale localization and function', Proceedings of the National Academy of Sciences of the United States of America, vol. 114, no. 45, pp. 12057-12062. https://doi.org/10.1073/pnas.1715341114

APA

Gerth, F., Jäpel, M., Pechstein, A., Kochlamazashvili, G., Lehmann, M., Puchkov, D., Onofri, F., Benfenati, F., Nikonenko, A. G., Fredrich, K., Shupliakov, O., Maritzen, T., Freund, C., & Haucke, V. (2017). Intersectin associates with synapsin and regulates its nanoscale localization and function. Proceedings of the National Academy of Sciences of the United States of America, 114(45), 12057-12062. https://doi.org/10.1073/pnas.1715341114

Vancouver

Gerth F, Jäpel M, Pechstein A, Kochlamazashvili G, Lehmann M, Puchkov D et al. Intersectin associates with synapsin and regulates its nanoscale localization and function. Proceedings of the National Academy of Sciences of the United States of America. 2017 Nov 7;114(45):12057-12062. https://doi.org/10.1073/pnas.1715341114

Author

Gerth, Fabian ; Jäpel, Maria ; Pechstein, Arndt ; Kochlamazashvili, Gaga ; Lehmann, Martin ; Puchkov, Dmytro ; Onofri, Franco ; Benfenati, Fabio ; Nikonenko, Alexander G. ; Fredrich, Kristin ; Shupliakov, Oleg ; Maritzen, Tanja ; Freund, Christian ; Haucke, Volker. / Intersectin associates with synapsin and regulates its nanoscale localization and function. In: Proceedings of the National Academy of Sciences of the United States of America. 2017 ; Vol. 114, No. 45. pp. 12057-12062.

BibTeX

@article{733e03fa6b51425fb3091b2645cc9788,
title = "Intersectin associates with synapsin and regulates its nanoscale localization and function",
abstract = "Neurotransmission is mediated by the exocytic release of neurotransmitters from readily releasable synaptic vesicles (SVs) at the active zone. To sustain neurotransmission during periods of elevated activity, release-ready vesicles need to be replenished from the reserve pool of SVs. The SV-associated synapsins are crucial for maintaining this reserve pool and regulate the mobilization of reserve pool SVs. How replenishment of release-ready SVs from the reserve pool is regulated and which other factors cooperate with synapsins in this process is unknown. Here we identify the endocytic multidomain scaffold protein intersectin as an important regulator of SV replenishment at hippocampal synapses. We found that intersectin directly associates with synapsin I through its Src-homology 3 A domain, and this association is regulated by an intramolecular switch within intersectin 1. Deletion of intersectin 1/2 in mice alters the presynaptic nanoscale distribution of synapsin I and causes defects in sustained neurotransmission due to defective SV replenishment. These phenotypes were rescued by wild-type intersectin 1 but not by a locked mutant of intersectin 1. Our data reveal intersectin as an autoinhibited scaffold that serves as a molecular linker between the synapsin-dependent reserve pool and the presynaptic endocytosis machinery.",
keywords = "Intramolecular regulation, Multidomain scaffold, Neurotransmission, NMR spectroscopy, Synaptic vesicles",
author = "Fabian Gerth and Maria J{\"a}pel and Arndt Pechstein and Gaga Kochlamazashvili and Martin Lehmann and Dmytro Puchkov and Franco Onofri and Fabio Benfenati and Nikonenko, {Alexander G.} and Kristin Fredrich and Oleg Shupliakov and Tanja Maritzen and Christian Freund and Volker Haucke",
year = "2017",
month = nov,
day = "7",
doi = "10.1073/pnas.1715341114",
language = "English",
volume = "114",
pages = "12057--12062",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "45",

}

RIS

TY - JOUR

T1 - Intersectin associates with synapsin and regulates its nanoscale localization and function

AU - Gerth, Fabian

AU - Jäpel, Maria

AU - Pechstein, Arndt

AU - Kochlamazashvili, Gaga

AU - Lehmann, Martin

AU - Puchkov, Dmytro

AU - Onofri, Franco

AU - Benfenati, Fabio

AU - Nikonenko, Alexander G.

AU - Fredrich, Kristin

AU - Shupliakov, Oleg

AU - Maritzen, Tanja

AU - Freund, Christian

AU - Haucke, Volker

PY - 2017/11/7

Y1 - 2017/11/7

N2 - Neurotransmission is mediated by the exocytic release of neurotransmitters from readily releasable synaptic vesicles (SVs) at the active zone. To sustain neurotransmission during periods of elevated activity, release-ready vesicles need to be replenished from the reserve pool of SVs. The SV-associated synapsins are crucial for maintaining this reserve pool and regulate the mobilization of reserve pool SVs. How replenishment of release-ready SVs from the reserve pool is regulated and which other factors cooperate with synapsins in this process is unknown. Here we identify the endocytic multidomain scaffold protein intersectin as an important regulator of SV replenishment at hippocampal synapses. We found that intersectin directly associates with synapsin I through its Src-homology 3 A domain, and this association is regulated by an intramolecular switch within intersectin 1. Deletion of intersectin 1/2 in mice alters the presynaptic nanoscale distribution of synapsin I and causes defects in sustained neurotransmission due to defective SV replenishment. These phenotypes were rescued by wild-type intersectin 1 but not by a locked mutant of intersectin 1. Our data reveal intersectin as an autoinhibited scaffold that serves as a molecular linker between the synapsin-dependent reserve pool and the presynaptic endocytosis machinery.

AB - Neurotransmission is mediated by the exocytic release of neurotransmitters from readily releasable synaptic vesicles (SVs) at the active zone. To sustain neurotransmission during periods of elevated activity, release-ready vesicles need to be replenished from the reserve pool of SVs. The SV-associated synapsins are crucial for maintaining this reserve pool and regulate the mobilization of reserve pool SVs. How replenishment of release-ready SVs from the reserve pool is regulated and which other factors cooperate with synapsins in this process is unknown. Here we identify the endocytic multidomain scaffold protein intersectin as an important regulator of SV replenishment at hippocampal synapses. We found that intersectin directly associates with synapsin I through its Src-homology 3 A domain, and this association is regulated by an intramolecular switch within intersectin 1. Deletion of intersectin 1/2 in mice alters the presynaptic nanoscale distribution of synapsin I and causes defects in sustained neurotransmission due to defective SV replenishment. These phenotypes were rescued by wild-type intersectin 1 but not by a locked mutant of intersectin 1. Our data reveal intersectin as an autoinhibited scaffold that serves as a molecular linker between the synapsin-dependent reserve pool and the presynaptic endocytosis machinery.

KW - Intramolecular regulation

KW - Multidomain scaffold

KW - Neurotransmission

KW - NMR spectroscopy

KW - Synaptic vesicles

UR - http://www.scopus.com/inward/record.url?scp=85033469426&partnerID=8YFLogxK

U2 - 10.1073/pnas.1715341114

DO - 10.1073/pnas.1715341114

M3 - Article

C2 - 29078407

AN - SCOPUS:85033469426

VL - 114

SP - 12057

EP - 12062

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 45

ER -

ID: 16798214