ArticleNature communications2024
Secretion of endoplasmic reticulum protein VAPB/ALS8 requires topological inversion.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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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.
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Who cites it
8 citing papers in PubMed.
- The zinc metalloprotease ZMPSTE24 binds a distinct topological isoform of the tail-anchored protein IFITM3.The Journal of biological chemistry · 2026Article
- Membrane Protein Insertion in Cells: Principles, Pathways, and Quality Control.Chemical reviews · 2026Review
- Large-scale exome analyses reveal new rare variant contributions in amyotrophic lateral sclerosis.Nature genetics · 2026Article
- The zinc metalloprotease ZMPSTE24 binds a distinct topological isoform of the tail-anchored protein IFITM3.bioRxiv : the preprint server for biology · 2026Article
- The Vap33 signaling axis precisely coordinates the timing of motoneuron dendritogenesis in neural map development.Nature communications · 2025Article
- Isolation and functional properties of highly-purified N-terminal domain of human NaPi2b by scalable "resin overload" technique.Analytical biochemistry · 2025Article
- Non-invasive tools for analysis of plasma membrane protein topology in living cells.Methods (San Diego, Calif.) · 2025Article
- Beyond Static Tethering at Membrane Contact Sites: Structural Dynamics and Functional Implications of VAP Proteins.Molecules (Basel, Switzerland) · 2025Review
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
VAMP-associated protein (VAP) is a type IV integral transmembrane protein at the endoplasmic reticulum (ER). Mutations in human VAPB/ALS8 are associated with amyotrophic lateral sclerosis (ALS). The N-terminal major sperm protein (MSP) domain of VAPB (Drosophila Vap33) is cleaved, secreted, and acts as a signaling ligand for several cell-surface receptors. Although extracellular functions of VAPB are beginning to be understood, it is unknown how the VAPB/Vap33 MSP domain facing the cytosol is secreted to the extracellular space. Here we show that Vap33 is transported to the plasma membrane, where the MSP domain is exposed extracellularly by topological inversion. The externalized MSP domain is cleaved by Matrix metalloproteinase 1/2 (Mmp1/2). Overexpression of Mmp1 restores decreased levels of extracellular MSP domain derived from ALS8-associated Vap33 mutants. We propose an unprecedented secretion mechanism for an ER-resident membrane protein, which may contribute to ALS8 pathogenesis.
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Registered trials
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.