Evidence map›Paper›PMID 38012142›Full record

ArticleNature communications2023

Synaptotagmin-7 outperforms synaptotagmin-1 to promote the formation of large, stable fusion pores via robust membrane penetration.

Kevin C Courtney, Taraknath Mandal, Nikunj Mehta, Lanxi Wu, Yueqi Li, Debasis Das, Qiang Cui, Edwin R Chapman

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.3field-weighted citation impact, top 21% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 6 citations in OpenAlex.

  1. Review
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  7. Review
  8. Lipid metabolism in the adrenal gland.Frontiers in endocrinology · 2025
    Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 5 institutions in 3 countries.

Kevin C CourtneyHoward Hughes Medical Institute and the Department of Neuroscience, University of Wisconsin, 1111 Highland Avenue, Madison, WI, 53705, USA.
Taraknath MandalDepartment of Chemistry, Boston University, Boston, MA, 02215, USA.
Nikunj MehtaHoward Hughes Medical Institute and the Department of Neuroscience, University of Wisconsin, 1111 Highland Avenue, Madison, WI, 53705, USA.ORCID http://orcid.org/0000-0001-7282-0428
Lanxi WuHoward Hughes Medical Institute and the Department of Neuroscience, University of Wisconsin, 1111 Highland Avenue, Madison, WI, 53705, USA.
Yueqi LiHoward Hughes Medical Institute and the Department of Neuroscience, University of Wisconsin, 1111 Highland Avenue, Madison, WI, 53705, USA.
Debasis DasHoward Hughes Medical Institute and the Department of Neuroscience, University of Wisconsin, 1111 Highland Avenue, Madison, WI, 53705, USA.
Qiang CuiDepartment of Chemistry, Boston University, Boston, MA, 02215, USA.
Edwin R ChapmanHoward Hughes Medical Institute and the Department of Neuroscience, University of Wisconsin, 1111 Highland Avenue, Madison, WI, 53705, USA. chapman@wisc.edu.ORCID http://orcid.org/0000-0001-9787-8140
Howard Hughes Medical Institute · USBoston University · USTata Institute of Fundamental Research · INUniversity of Science and Technology of China · CNWest Virginia University · US

Funding

Synaptotagmin C2B Domain as a Ca2+ Sensing ModuleR01MH061876 · NIMH · UNIVERSITY OF WISCONSIN-MADISON · PI Edwin R Chapman · 2002 to 2026
$7.7M
Structure and dynamics of exocytotic fusion poresR35NS097362 · NINDS · UNIVERSITY OF WISCONSIN-MADISON · PI CHAPMAN, EDWIN R · 2017 to 2024
$4.6M
NIMH NIH HHS R01 MH061876NINDS NIH HHS R35 NS097362
6 · The paper itself

Abstract

Synaptotagmin-1 and synaptotagmin-7 are two prominent calcium sensors that regulate exocytosis in neuronal and neuroendocrine cells. Upon binding calcium, both proteins partially penetrate lipid bilayers that bear anionic phospholipids, but the specific underlying mechanisms that enable them to trigger exocytosis remain controversial. Here, we examine the biophysical properties of these two synaptotagmin isoforms and compare their interactions with phospholipid membranes. We discover that synaptotagmin-1-membrane interactions are greatly influenced by membrane order; tight packing of phosphatidylserine inhibits binding due to impaired membrane penetration. In contrast, synaptotagmin-7 exhibits robust membrane binding and penetration activity regardless of phospholipid acyl chain structure. Thus, synaptotagmin-7 is a super-penetrator. We exploit these observations to specifically isolate and examine the role of membrane penetration in synaptotagmin function. Using nanodisc-black lipid membrane electrophysiology, we demonstrate that membrane penetration is a critical component that underlies how synaptotagmin proteins regulate reconstituted, exocytic fusion pores in response to calcium.

Indexed as

CalciumSynaptotagmin ICalcium-Binding ProteinsCell MembraneExocytosisPhospholipidsSynaptotagminsCalciumCalcium-Binding ProteinsPhospholipidsSynaptotagmin ISynaptotagmins

Identifiers

PMID38012142
PMCPMC10681989
OpenAlexW4389049727

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.