Evidence map›Paper›PMID 27307044›Full record

ArticleThe Journal of biological chemistry2016

Structural Elements in the Transmembrane and Cytoplasmic Domains of the Metal Transporter SLC30A10 Are Required for Its Manganese Efflux Activity.

Charles E Zogzas, Michael Aschner, Somshuvra Mukhopadhyay

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.

0numbers the graph read from it
0cells of the map it votes in
52citing papers in PubMed
6.7field-weighted citation impact, top 3% 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

52 citing papers in PubMed, 74 citations in OpenAlex.

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  12. PHD2 enzyme is an intracellular manganese sensor that initiates the homeostatic response against elevated manganese.Proceedings of the National Academy of Sciences of the United States of America · 2024
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  19. Role of excretion in manganese homeostasis and neurotoxicity: a historical perspective.American journal of physiology. Gastrointestinal and liver physiology · 2022
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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

3 authors at 2 institutions in 1 country.

Charles E ZogzasFrom the Division of Pharmacology and Toxicology, College of Pharmacy, Institute for Cellular and Molecular Biology, and Institute for Neuroscience, University of Texas at Austin, Austin, Texas 78712 and.
Michael Aschnerthe Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York 10461.
Somshuvra MukhopadhyayFrom the Division of Pharmacology and Toxicology, College of Pharmacy, Institute for Cellular and Molecular Biology, and Institute for Neuroscience, University of Texas at Austin, Austin, Texas 78712 and som@austin.utexas.edu.
The University of Texas at Austin · USAlbert Einstein College of Medicine · US

Funding

Regulation of manganese homeostasis and detoxification by SLC30A10R01ES024812 · NIEHS · UNIVERSITY OF TEXAS AT AUSTIN · PI Somshuvra Mukhopadhyay · 2016 to 2026
$5.7M
Role of Mechanisms of Efflux in Manganese Homeostasis and DetoxificationR00ES020844 · NIEHS · UNIVERSITY OF TEXAS AT AUSTIN · PI MUKHOPADHYAY, SOMSHUVRA · 2013 to 2015
$747k
NIEHS NIH HHS R00 ES020844NIEHS NIH HHS R01 ES024812
6 · The paper itself

Abstract

Homozygous mutations in SLC30A10 lead to the development of familial manganese-induced parkinsonism. We previously demonstrated that SLC30A10 is a cell surface-localized manganese efflux transporter, and parkinsonism-causing mutations block its trafficking and efflux activity. Interestingly, other transporters in the SLC30 family mediate zinc efflux. Determining the mechanisms that allow SLC30A10 to transport manganese, which are unclear, is essential to understand its role in parkinsonism. Here, we generated a predicted structure of SLC30A10, based on the structure of the bacterial zinc transporter YiiP, and performed functional studies. In YiiP, side chains of residues Asp-45 and Asp-49 in the second and His-153 and Asp-157 in the fifth transmembrane segments coordinate zinc and are required for transport. In SLC30A10, the corresponding residues are Asn-43 and Asp-47 in the second and His-244 and Asp-248 in the fifth transmembrane segments. Surprisingly, although alanine substitution of Asp-248 abolished manganese efflux, that of Asn-43 and Asp-47 did not. Instead, side chains of charged or polar residues adjacent to Asp-248 in the first (Glu-25) or fourth (Asn-127) transmembrane segments were required. Further analyses revealed that residues His-333 and His-350 in the cytoplasmic C-terminal domain were required for full activity. However, the C-terminal domain failed to transfer manganese transport capability to a related zinc transporter. Overall, our results indicate that residues in the transmembrane and C-terminal domains together confer optimal manganese transport capability to SLC30A10 and suggest that the mechanism of ion coordination in the transmembrane domain of SLC30A10 may be substantially different from that in YiiP/other SLC30 proteins.

Indexed as

Cation Transport ProteinsManganeseEscherichia coli ProteinsHeLa CellsHumansIon TransportMembrane Transport ProteinsProtein DomainsStructural Homology, ProteinZinc Transporter 8Cation Transport ProteinsEscherichia coli ProteinsManganeseMembrane Transport ProteinsSLC30A8 protein, humanYiiP protein, E coliZinc Transporter 8intracellular traffickingmanganesemetal homeostasisneurodegenerative diseasestructure-functiontransporterzinc

Identifiers

PMID27307044
PMCPMC4965547
OpenAlexW2444460391

What OpenQuestion holds

Textmetadata
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.