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Surfaceome dynamics reveal proteostasis-independent reorganization of neuronal surface proteins during development and synaptic plasticity

van Oostrum, Marc, Campbell, Benjamin, Seng, Charlotte, Müller, Maik, tom Dieck, Susanne, Hammer, Jacqueline, Pedrioli, Patrick G. A., Földy, Csaba, Tyagarajan, Shiva K., Wollscheid, Bernd·2020·Nature Communications
DOI 10.1038/s41467-020-18494-6PMC PMC7536423

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Abstract

Neurons are highly compartmentalized cells with tightly controlled subcellular protein organization. While brain transcriptome, connectome and global proteome maps are being generated, system-wide analysis of temporal protein dynamics at the subcellular level are currently lacking. Here, we perform a temporally-resolved surfaceome analysis of primary neuron cultures and reveal dynamic surface protein clusters that reflect the functional requirements during distinct stages of neuronal development. Direct comparison of surface and total protein pools during development and homeostatic synaptic scaling demonstrates system-wide proteostasis-independent remodeling of the neuronal surface, illustrating widespread regulation on the level of surface trafficking. Finally, quantitative analysis of the neuronal surface during chemical long-term potentiation (cLTP) reveals fast externalization of diverse classes of surface proteins beyond the AMPA receptor, providing avenues to investigate the requirement of exocytosis for LTP. Our resource (neurosurfaceome.ethz.ch) highlights the importance of subcellular resolution for systems-level understanding of cellular processes.

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Crossref · 10.1038/s41467-020-18494-6

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  • Extensive changes in the neuronal surface proteome upon cLTP are mediated by the delivery of membrane proteins from intracellular compartments.

    “recent findings that show extensive changes in the neuronal surface proteome upon cLTP, which are mediated by the delivery of membrane proteins from intracellular compartments”

    From PI(3)P coordinates SNX17- and SNX27-dependent protein recycling for long-term synaptic plasticity (2025) · cites this paper as van Oostrum et al., 2020

    The Results section (‘Surface trafficking of diverse cargo during cLTP,’ Fig. 6) reports extensive surface-protein changes and says the increased surface abundance of AMPA receptors indicates exocytosis. It does not establish that delivery from intracellular compartments mediates the broader set of changes; the Discussion says the other proteins with increased surface abundance *could* account for the role of exocytosis. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Endocytic recycling is a key mechanism by which neurons control the composition of surface receptors, adhesion molecules, and transporters in response to synaptic activity.

    “Endocytic recycling, in which internalized surface proteins are routed back to the plasma membrane, is a key mechanism by which neurons control the composition of surface receptors, adhesion molecules, and transporters in response to synaptic activity”

    From Dual endomembrane recycling pathways function in parallel to support synapse maintenance and plasticity (2025) · cites this paper as van Oostrum et al., 2020

    The Results sections on surface-abundance profiles and differential regulation identify endosomal recycling as one of several processes that help control neuronal surface proteins and synaptic plasticity. The cLTP Results report activity-related surface changes in receptors, adhesion molecules, and solute carriers. The paper does not establish that endocytic recycling specifically drives those changes or is the key mechanism for them; it also discusses biosynthesis, degradation, and other surface trafficking. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Multiple types of proteins undergo rapid externalization in response to cLTP.

    “A recent quantitative analysis of the neuronal surface proteome demonstrated that multiple types of proteins undergo rapid externalization in response to cLTP (van Oostrum et al., 2020).”

    From PI(3)P coordinates SNX17- and SNX27-dependent protein recycling for long-term synaptic plasticity (2025) · cites this paper as van Oostrum et al., 2020

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Authors
van Oostrum, M., Campbell, B., Seng, C., Müller, M., tom Dieck, S., Hammer, J., Pedrioli, P. G. A., Földy, C., Tyagarajan, S. K., & Wollscheid, B.
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2020-10-05
Volume
11
Issue
1
ISSN
2041-1723
DOI
10.1038/s41467-020-18494-6
PMC
PMC7536423
Cited by
46
References
17
Language
en
Update notices
correction (2020-11-06)
Licence
Funders
  • Eidgenössische Technische Hochschule Zürich (ETH-25 15-2)
  • Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (31003A_160259)

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