DOI: 10.1083/jcb.201206063. Cryo–electron tomography reveals a critical role of RIM1α in synaptic vesicle tethering

Cryo–electron tomography reveals a critical role of RIM1α in synaptic vesicle tethering

10.1083/jcb.201206063

Crossref journal-article

Rockefeller University Press

Journal of Cell Biology (291)

Abstract

Synaptic vesicles are embedded in a complex filamentous network at the presynaptic terminal. Before fusion, vesicles are linked to the active zone (AZ) by short filaments (tethers). The identity of the molecules that form and regulate tethers remains unknown, but Rab3-interacting molecule (RIM) is a prominent candidate, given its central role in AZ organization. In this paper, we analyzed presynaptic architecture of RIM1α knockout (KO) mice by cryo–electron tomography. In stark contrast to previous work on dehydrated, chemically fixed samples, our data show significant alterations in vesicle distribution and AZ tethering that could provide a structural basis for the functional deficits of RIM1α KO synapses. Proteasome inhibition reversed these structural defects, suggesting a functional recovery confirmed by electrophysiological recordings. Altogether, our results not only point to the ubiquitin–proteasome system as an important regulator of presynaptic architecture and function but also show that the tethering machinery plays a critical role in exocytosis, converging into a structural model of synaptic vesicle priming by RIM1α.

Bibliography

FernÃ¡ndez-Busnadiego, R., Asano, S., Oprisoreanu, A.-M., Sakata, E., Doengi, M., Kochovski, Z., ZÃ¼rner, M., Stein, V., Schoch, S., Baumeister, W., & LuÄiÄ, V. (2013). Cryoâelectron tomography reveals a critical role of RIM1Î± in synaptic vesicle tethering. Journal of Cell Biology, 201(5), 725â740.

Authors 11

Rubén Fernández-Busnadiego (first)
Shoh Asano (additional)
Ana-Maria Oprisoreanu (additional)
Eri Sakata (additional)
Michael Doengi (additional)
Zdravko Kochovski (additional)
Magdalena Zürner (additional)
Valentin Stein (additional)
Susanne Schoch (additional)
Wolfgang Baumeister (additional)
Vladan Lučić (additional)

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Dates

Type	When
Created	12 years, 3 months ago (May 27, 2013, 11:42 a.m.)
Deposited	2 years, 1 month ago (July 23, 2023, 1:50 a.m.)
Indexed	3 weeks ago (Aug. 6, 2025, 9:09 a.m.)
Issued	12 years, 3 months ago (May 27, 2013)
Published	12 years, 3 months ago (May 27, 2013)
Published Online	12 years, 3 months ago (May 27, 2013)
Published Print	12 years, 3 months ago (May 27, 2013)

Funders 0

None

BibTeX

@article{Fern_ndez_Busnadiego_2013, title={Cryo–electron tomography reveals a critical role of RIM1α in synaptic vesicle tethering}, volume={201}, ISSN={0021-9525}, url={http://dx.doi.org/10.1083/jcb.201206063}, DOI={10.1083/jcb.201206063}, number={5}, journal={Journal of Cell Biology}, publisher={Rockefeller University Press}, author={Fernández-Busnadiego, Rubén and Asano, Shoh and Oprisoreanu, Ana-Maria and Sakata, Eri and Doengi, Michael and Kochovski, Zdravko and Zürner, Magdalena and Stein, Valentin and Schoch, Susanne and Baumeister, Wolfgang and Lučić, Vladan}, year={2013}, month=may, pages={725–740} }

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        [
          2013,
          5,
          27
        ]
      ]
    }
  },
  "URL": "http://dx.doi.org/10.1083/jcb.201206063",
  "relation": {},
  "ISSN": [
    "1540-8140",
    "0021-9525"
  ],
  "subject": [],
  "published": {
    "date-parts": [
      [
        2013,
        5,
        27
      ]
    ]
  }
}