Evidence map›Paper›PMID 35353806›Full record

ArticlePLoS biology2022

TMED2 binding restricts SMO to the ER and Golgi compartments.

Giulio Di Minin, Markus Holzner, Alice Grison, Charles E Dumeau, Wesley Chan, Asun Monfort, Loydie A Jerome-Majewska, Henk Roelink, Anton Wutz

Open access · goldAbstract read
In one paragraph

Article in PLoS biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing 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

12 citing papers in PubMed, 16 citations in OpenAlex.

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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

9 authors at 4 institutions in 3 countries.

Giulio Di MininInstitute of Molecular Health Sciences, Department of Biology, Swiss Federal Institute of Technology ETH Hönggerberg, Zurich, Switzerland.ORCID 0000-0003-4356-6939
Markus HolznerInstitute of Molecular Health Sciences, Department of Biology, Swiss Federal Institute of Technology ETH Hönggerberg, Zurich, Switzerland.
Alice GrisonDepartment of Biomedicine, University of Basel, Basel, Switzerland.
Charles E DumeauInstitute of Molecular Health Sciences, Department of Biology, Swiss Federal Institute of Technology ETH Hönggerberg, Zurich, Switzerland.
Wesley ChanDepartment Anatomy and Cell Biology, Human Genetics and McGill University, Montreal, Canada.
Asun MonfortInstitute of Molecular Health Sciences, Department of Biology, Swiss Federal Institute of Technology ETH Hönggerberg, Zurich, Switzerland.
Loydie A Jerome-MajewskaDepartment Anatomy and Cell Biology, Human Genetics and McGill University, Montreal, Canada.ORCID 0000-0002-5047-4058
Henk RoelinkDepartment of Molecular and Cell Biology, University of California, Berkeley, California, United States of America.
Anton WutzInstitute of Molecular Health Sciences, Department of Biology, Swiss Federal Institute of Technology ETH Hönggerberg, Zurich, Switzerland.ORCID 0000-0002-4377-6330
École Polytechnique Fédérale de Lausanne · CHMcGill University · CAUniversity of Basel · CHUniversity of California, Berkeley · US

Funding

Sonic Hedgehog is a Calcium-regulated Zinc peptidaseR01GM117090 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI ROELINK, HENK · 2016 to 2022
$1.9M
NIGMS NIH HHS R01 GM117090
6 · The paper itself

Abstract

Hedgehog (HH) signaling is important for embryonic pattering and stem cell differentiation. The G protein-coupled receptor (GPCR) Smoothened (SMO) is the key HH signal transducer modulating both transcription-dependent and transcription-independent responses. We show that SMO protects naive mouse embryonic stem cells (ESCs) from dissociation-induced cell death. We exploited this SMO dependency to perform a genetic screen in haploid ESCs where we identify the Golgi proteins TMED2 and TMED10 as factors for SMO regulation. Super-resolution microscopy shows that SMO is normally retained in the endoplasmic reticulum (ER) and Golgi compartments, and we demonstrate that TMED2 binds to SMO, preventing localization to the plasma membrane. Mutation of TMED2 allows SMO accumulation at the plasma membrane, recapitulating early events after HH stimulation. We demonstrate the physiologic relevance of this interaction in neural differentiation, where TMED2 functions to repress HH signal strength. Identification of TMED2 as a binder and upstream regulator of SMO opens the way for unraveling the events in the ER-Golgi leading to HH signaling activation.

Indexed as

Hedgehog ProteinsReceptors, G-Protein-CoupledAnimalsCell MembraneEndoplasmic ReticulumMembrane ProteinsMiceSignal TransductionSmoothened ReceptorVesicular Transport ProteinsHedgehog ProteinsMembrane ProteinsReceptors, G-Protein-CoupledSmoothened ReceptorSmo protein, mouseTmed2 protein, mouseVesicular Transport Proteins

Identifiers

PMID35353806
PMCPMC9000059
OpenAlexW4221059399

What OpenQuestion 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 OpenQuestion graph.