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Cited by 20Lipid metabolism and biosynthesisCellular transport and secretionLipid Membrane Structure and Behavior

Co-translational biogenesis of lipid droplet integral membrane proteins

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Leznicki, Pawel, Schneider, Hayden O., Harvey, Jada V., Shi, Wei Q., High, Stephen·2022·Journal of Cell Science
DOI 10.1242/jcs.259220PMC PMC8627552

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Abstract

Membrane proteins destined for lipid droplets (LDs), a major intracellular storage site for neutral lipids, are inserted into the endoplasmic reticulum (ER) and then trafficked to LDs where they reside in a hairpin loop conformation. Here, we show that LD membrane proteins can be delivered to the ER either co- or post-translationally and that their membrane-embedded region specifies pathway selection. The co-translational route for LD membrane protein biogenesis is insensitive to a small molecule inhibitor of the Sec61 translocon, Ipomoeassin F, and instead relies on the ER membrane protein complex (EMC) for membrane insertion. This route may even result in a transient exposure of the short N termini of some LD membrane proteins to the ER lumen, followed by putative topological rearrangements that would enable their transmembrane segment to form a hairpin loop and N termini to face the cytosol. Our study reveals an unexpected complexity to LD membrane protein biogenesis and identifies a role for the EMC during their co-translational insertion into the ER.

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  • EMC has been implicated in topological decision-making of ER hairpin proteins that target lipid droplets.

    “EMC has also been implicated in topological decision-making of ER hairpin proteins that target LDs (Leznicki et al., 2022).”

    From APOE traffics to astrocyte lipid droplets and modulates triglyceride saturation and droplet size (2024) · cites this paper as Leznicki et al., 2022

    The Results section (‘Co-translational insertion of LD membrane proteins relies on the EMC’; page unavailable) implicates EMC in inserting lipid-droplet proteins into the ER with a transient membrane-spanning orientation. The Discussion says EMC may not discriminate between proteins that retain that orientation and those that later form hairpins, and leaves the mechanism of that transition unresolved. Thus, the paper supports EMC involvement in an initial topological state, but not a demonstrated role in deciding the final hairpin topology. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

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Sorted by citations

Authors
Leznicki, P., Schneider, H. O., Harvey, J. V., Shi, W. Q., & High, S.
Affiliations
  • School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, M13 9PT, UK
  • Ball State University (US)
  • University of Manchester (GB)
Corresponding author
High, Stephen
ORCID
Venue
Journal of Cell Science
Publisher
The Company of Biologists
Published
2021-11-02
Volume
135
Issue
5
ISSN
  • 0021-9533 (ISSN-L)
  • 1477-9137
DOI
10.1242/jcs.259220
PMC
PMC8627552
OpenAlex
W3200590774
Cited by
20
References
1
Citations by year
2026: 2 · 2025: 8 · 2024: 2 · 2023: 4 · 2022: 3 · 2021: 1
FWCI
1.03
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Cell Science (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research Explorer (The University of Manchester) (submittedVersion)
Funders
  • Wellcome Trust (204957/Z/16/Z)
  • National Institute of General Medical Sciences (2R15GM116032-02A1)
  • National Institutes of Health (2R15GM116032-02A1)
  • Ball State University
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
Keywords
endoplasmic reticulum, Sec61 translocon, membrane protein biogenesis, protein topology, neutral lipid storage
MeSH terms
SEC Translocation Channels, Cytosol, Endoplasmic Reticulum, Membrane Proteins, Lipid Droplets

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

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