Evidence map›Paper›PMID 41238049›Full record

ArticleNeuroscience2025

Dual endomembrane recycling pathways function in parallel to support synapse maintenance and plasticity.

Garrett D Chavis, Pilar Rivero-Ríos, Tunahan Uygun, Takao Tsukahara, Takayuki Hayami, Grace Y Lee, Minseo Lee, Christina Pace, Francesca N Czesak, Kathryn L Hilde and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuroscience, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors.

Garrett D ChavisDepartment of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA; Molecular and Integrative Physiology Graduate Program, University, Ann Arbor, MI 48109, USA; Michigan Neuroscience Institute, University of Michigan, Ann Arbor, MI 48109, USA.
Pilar Rivero-RíosLife Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA; Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
Tunahan UygunLife Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA; Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
Takao TsukaharaDepartment of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA; Michigan Neuroscience Institute, University of Michigan, Ann Arbor, MI 48109, USA; Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA.
Takayuki HayamiDepartment of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA; Michigan Neuroscience Institute, University of Michigan, Ann Arbor, MI 48109, USA.
Grace Y LeeDepartment of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA.
Minseo LeeDepartment of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA.
Christina PaceDepartment of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA.
Francesca N CzesakMichigan Neuroscience Institute, University of Michigan, Ann Arbor, MI 48109, USA; Neuroscience Graduate Program, University of Michigan, Ann Arbor, MI 48109, USA.
Kathryn L HildeMichigan Neuroscience Institute, University of Michigan, Ann Arbor, MI 48109, USA; Department of Psychiatry, University of Michigan, Ann Arbor, MI 48109, USA.
Fei LiMichigan Neuroscience Institute, University of Michigan, Ann Arbor, MI 48109, USA; Department of Psychiatry, University of Michigan, Ann Arbor, MI 48109, USA.
Shigeki IwaseMichigan Neuroscience Institute, University of Michigan, Ann Arbor, MI 48109, USA; Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA; Neuroscience Graduate Program, University of Michigan, Ann Arbor, MI 48109, USA; Department of Pediatrics, University of Michigan, Ann Arbor, MI 48109, USA.
Geoffrey G MurphyDepartment of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA; Molecular and Integrative Physiology Graduate Program, University, Ann Arbor, MI 48109, USA; Michigan Neuroscience Institute, University of Michigan, Ann Arbor, MI 48109, USA; Neuroscience Graduate Program, University of Michigan, Ann Arbor, MI 48109, USA.
Jonathan D MorrowNeuroscience Graduate Program, University of Michigan, Ann Arbor, MI 48109, USA; Department of Psychiatry, University of Michigan, Ann Arbor, MI 48109, USA.
Huda AkilMichigan Neuroscience Institute, University of Michigan, Ann Arbor, MI 48109, USA; Neuroscience Graduate Program, University of Michigan, Ann Arbor, MI 48109, USA; Department of Psychiatry, University of Michigan, Ann Arbor, MI 48109, USA.
Lois S WeismanMichigan Neuroscience Institute, University of Michigan, Ann Arbor, MI 48109, USA; Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA; Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA; Neuroscience Graduate Program, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: lweisman@umich.edu.
Michael A SuttonDepartment of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA; Molecular and Integrative Physiology Graduate Program, University, Ann Arbor, MI 48109, USA; Michigan Neuroscience Institute, University of Michigan, Ann Arbor, MI 48109, USA; Neuroscience Graduate Program, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: masutton@umich.edcu.

Funding

Research Education ComponentP30AG072931 · NIA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Henry L Paulson · 2021 to 2026
$26.5M
A Neuron-specific Methyl-histone Regulatory ComplexR01NS116008 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Shigeki Iwase · 2020 to 2026
$3.6M
Regulation of parallel recycling pathways at synaptic sitesR01NS129198 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Michael Mark Alexander Sutton, Lois S Weisman · 2022 to 2026
$2.4M
NIA NIH HHS P30 AG072931NINDS NIH HHS R01 NS116008NINDS NIH HHS R01 NS129198
6 · The paper itself

Abstract

The SNX27-Retromer and more recently discovered SNX17-Retriever complexes are key drivers in recycling internalized cargoes back to the cell surface in eukaryotic cells, but the extent to which these pathways have unique or redundant roles in neurons is not known. Here, we show similar, but non-overlapping, roles of the SNX17-Retriever and SNX27-Retromer pathways in the maintenance and plasticity of excitatory synapses. We find that in vivo disruption of either pathway in developing rats leads to a marked loss of excitatory synapses in CA1 pyramidal neurons, a phenotype that is recapitulated in cultured hippocampal neurons. Further analysis in cultured neurons confirms that SNX17 and SNX27 colocalize prominently with each other and Retriever/Retromer in early endosomes, indicating a largely shared cellular localization of the two pathways. Interestingly, coordinate disruption of both pathways produced an additive loss of excitatory synapses, suggesting parallel roles in synapse maintenance. We further show that certain cargoes are specific for each pathway and that both recycling pathways are essential for numerous forms of synaptic plasticity, including long-term potentiation (LTP), long-term depression (LTD), and homeostatic synaptic scaling. Together, our results support a model where the SNX17-Retriever and SNX27-Retromer pathways function largely in parallel at synapses, with their combinatorial action a key requirement for long-lasting forms of synaptic plasticity.

Indexed as

EndosomesNeuronal PlasticitySorting NexinsSynapsesAnimalsCells, CulturedHippocampusMaleNeuronsRatsRats, Sprague-DawleySorting NexinsEndocytic traffickingProtein recyclingRetrieverRetromerSNX17SNX27SynapseSynaptic plasticity

Identifiers

PMID41238049
PMCPMC13052551

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Registered trials

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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 OpenQuestion graph.