Evidence map›Paper›PMID 36640319›Full record

ArticleCell reports2023

The Get1/2 insertase forms a channel to mediate the insertion of tail-anchored proteins into the ER.

Paul Heo, Jacob A Culver, Jennifer Miao, Frederic Pincet, Malaiyalam Mariappan

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.5field-weighted citation impact, top 37% 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

4 citing papers in PubMed, 7 citations in OpenAlex.

  1. Review
  2. A phosphoinositide-mediated switch of GET pathway receptor dimerization inProceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  3. Article
  4. Article
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

5 authors at 2 institutions in 3 countries.

Paul HeoLaboratoire de Physique de l'Ecole Normale Supérieure, ENS, Université PSL, CNRS, Sorbonne Université, Université de Paris, 75005 Paris, France; Institute of Psychiatry and Neuroscience of Paris, INSERM U1266, 75014 Paris, France. Electronic address: paul.heo@inserm.fr.
Jacob A CulverDepartment of Cell Biology, Yale School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA; Nanobiology Institute, Yale University West Campus, West Haven, CT 06516, USA.
Jennifer MiaoDepartment of Cell Biology, Yale School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA; Nanobiology Institute, Yale University West Campus, West Haven, CT 06516, USA.
Frederic PincetLaboratoire de Physique de l'Ecole Normale Supérieure, ENS, Université PSL, CNRS, Sorbonne Université, Université de Paris, 75005 Paris, France. Electronic address: frederic.pincet@ens.fr.
Malaiyalam MariappanDepartment of Cell Biology, Yale School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA; Nanobiology Institute, Yale University West Campus, West Haven, CT 06516, USA. Electronic address: malaiyalam.mariappan@yale.edu.
Yale University · USCentre National de la Recherche Scientifique · FR

Funding

The mechanism of Ire1-mediated mRNA cleavage during endoplasmic reticulum stressR01GM117386 · NIGMS · YALE UNIVERSITY · PI MARIAPPAN, MALAIYALAM · 2016 to 2024
$3.0M
Retro-proteomics to identify misfolded proteins from the ER and their quality control pathwaysR21AG056800 · NIA · YALE UNIVERSITY · PI MARIAPPAN, MALAIYALAM · 2018 to 2019
$461k
NIA NIH HHS R21 AG056800NIGMS NIH HHS R01 GM117386
6 · The paper itself

Abstract

Tail-anchored (TA) proteins contain a single C-terminal transmembrane domain (TMD) that is captured by the cytosolic Get3 in yeast (TRC40 in humans). Get3 delivers TA proteins to the Get1/2 complex for insertion into the endoplasmic reticulum (ER) membrane. How Get1/2 mediates insertion of TMDs of TA proteins into the membrane is poorly understood. Using bulk fluorescence and microfluidics assays, we show that Get1/2 forms an aqueous channel in reconstituted bilayers. We estimate the channel diameter to be ∼2.5 nm wide, corresponding to the circumference of two Get1/2 complexes. We find that the Get3 binding can seal the Get1/2 channel, which dynamically opens and closes. Our mutation analysis further shows that the Get1/2 channel activity is required to release TA proteins from Get3 for insertion into the membrane. Hence, we propose that the Get1/2 channel functions as an insertase for insertion of TMDs and as a translocase for translocation of C-terminal hydrophilic segments.

Indexed as

Saccharomyces cerevisiae ProteinsEndoplasmic ReticulumGuanine Nucleotide Exchange FactorsHumansMembrane ProteinsProtein TransportSaccharomyces cerevisiaeGET1 protein, S cerevisiaeGuanine Nucleotide Exchange FactorsMembrane ProteinsSaccharomyces cerevisiae ProteinschannelCP: Cell biologyCP: Molecular biologymembrane protein insertionprotein translocationtail-anchored proteins

Identifiers

PMID36640319
PMCPMC9932932
OpenAlexW4313530061

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.