Evidence map›Paper›PMID 31417168›Full record

ArticleScientific reports2019

The WRB Subunit of the Get3 Receptor is Required for the Correct Integration of its Partner CAML into the ER.

Hugo J F Carvalho, Andrea Del Bondio, Francesca Maltecca, Sara F Colombo, Nica Borgese

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.5field-weighted citation impact, top 18% 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

14 citing papers in PubMed, 25 citations in OpenAlex.

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  11. Endoplasmic reticulum membrane receptors of the GET pathway are conserved throughout eukaryotes.Proceedings of the National Academy of Sciences of the United States of America · 2021
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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

5 authors at 2 institutions in 2 countries.

Hugo J F CarvalhoConsiglio Nazionale delle Ricerche Institute of Neuroscience and BIOMETRA Department, Università degli Studi di Milano, I-20129, Milan, Italy.
Andrea Del BondioDivision of Neuroscience, Ospedale San Raffaele, I-20132, Milan, Italy.
Francesca MalteccaDivision of Neuroscience, Ospedale San Raffaele, I-20132, Milan, Italy.
Sara F ColomboConsiglio Nazionale delle Ricerche Institute of Neuroscience and BIOMETRA Department, Università degli Studi di Milano, I-20129, Milan, Italy. sara.colombo@in.cnr.it.
Nica BorgeseConsiglio Nazionale delle Ricerche Institute of Neuroscience and BIOMETRA Department, Università degli Studi di Milano, I-20129, Milan, Italy. nica.borgese@in.cnr.it.ORCID http://orcid.org/0000-0002-7537-3974
University of Milan · ITIRCCS Ospedale San Raffaele · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Calcium-modulating cyclophilin ligand (CAML), together with Tryptophan rich basic protein (WRB, Get1 in yeast), constitutes the mammalian receptor for the Transmembrane Recognition Complex subunit of 40 kDa (TRC40, Get3 in yeast), a cytosolic ATPase with a central role in the post-translational targeting pathway of tail-anchored (TA) proteins to the endoplasmic reticulum (ER) membrane. CAML has also been implicated in other cell-specific processes, notably in immune cell survival, and has been found in molar excess over WRB in different cell types. Notwithstanding the stoichiometric imbalance, WRB and CAML depend strictly on each other for expression. Here, we investigated the mechanism by which WRB impacts CAML levels. We demonstrate that CAML, generated in the presence of sufficient WRB levels, is inserted into the ER membrane with three transmembrane segments (TMs) in its C-terminal region. By contrast, without sufficient levels of WRB, CAML fails to adopt this topology, and is instead incompletely integrated to generate two aberrant topoforms; these congregate in ER-associated clusters and are degraded by the proteasome. Our results suggest that WRB, a member of the recently proposed Oxa1 superfamily, acts catalytically to assist the topogenesis of CAML and may have wider functions in membrane biogenesis than previously appreciated.

Indexed as

Protein Interaction Domains and MotifsAdaptor Proteins, Signal TransducingArsenite Transporting ATPasesBiomarkersEndoplasmic ReticulumFluorescent Antibody TechniqueHumansMembrane ProteinsProteasome Endopeptidase ComplexProtein BindingProtein TransportProteolysisAdaptor Proteins, Signal TransducingArsenite Transporting ATPasesBiomarkersCAMLG protein, humanGET3 protein, humanMembrane ProteinsProteasome Endopeptidase Complex

Identifiers

PMID31417168
PMCPMC6695381
OpenAlexW2967915637

What OpenQuestion holds

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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.