ArticlePloS one2012
Analysis of the key elements of FFAT-like motifs identifies new proteins that potentially bind VAP on the ER, including two AKAPs and FAPP2.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 105 citations in OpenAlex.
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- Neuro-glial lipid imbalance in a Drosophila model of amyotrophic lateral sclerosis 8.Acta neuropathologica communications · 2026Article
- Glycolipid transfer protein modulates vesicular trafficking from the endoplasmic reticulum in HeLa cells.The Journal of biological chemistry · 2026Article
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- The Vap33 signaling axis precisely coordinates the timing of motoneuron dendritogenesis in neural map development.Nature communications · 2025Article
- Acyl-CoA-binding protein AcbdA is required for peroxisome hitchhiking on early endosomes inMolecular biology of the cell · 2025Article
- Elevated synaptic PKA activity and abnormal striatal dopamine signaling in Akap11 mutant mice, a genetic model of schizophrenia and bipolar disorder.Nature communications · 2025Article
- Elevated synaptic PKA activity and abnormal striatal dopamine signaling inbioRxiv : the preprint server for biology · 2025Article
- Emerging roles of lipid transfer protein dimerization.Journal of cell science · 2025Review
- Multiple cAMP/PKA complexes at the STIM1 ER/PM junction specified by E-Syt1 and E-Syt2 reciprocally gates ANO1 (TMEM16A) via CaNature communications · 2025Article
- Lysosome-Mitochondrial Crosstalk in Cellular Stress and Disease.Antioxidants (Basel, Switzerland) · 2025Review
- Secretion of endoplasmic reticulum protein VAPB/ALS8 requires topological inversion.Nature communications · 2024Article
- Molecular regulation of calcium-sensing receptor (CaSR)-mediated signaling.Chronic diseases and translational medicine · 2024Review
- USP20 deubiquitinates and stabilizes the reticulophagy receptor RETREG1/FAM134B to drive reticulophagy.Autophagy · 2024Article
- Phosphorylation of ELYS promotes its interaction with VAPB at decondensing chromosomes during mitosis.EMBO reports · 2024Article
- Neuronal ER-plasma membrane junctions couple excitation to CaNature communications · 2023Article
- Endoplasmic Reticulum Membrane Contact Sites, Lipid Transport, and Neurodegeneration.Cold Spring Harbor perspectives in biology · 2023Review
- MOSPD2 is an endoplasmic reticulum-lipid droplet tether functioning in LD homeostasis.The Journal of cell biology · 2022Article
- Organelle transporters and inter-organelle communication as drivers of metabolic regulation and cellular homeostasis.Molecular metabolism · 2022Review
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
backgroundTwo phenylalanines (FF) in an acidic tract (FFAT)-motifs were originally described as having seven elements: an acidic flanking region followed by 6 residues (EFFDA-E). Such motifs are found in several lipid transfer protein (LTP) families, and they interact with a protein on the cytosolic face of the ER called vesicle-associated membrane protein-associated protein (VAP). Mutation of which causes ER stress and motor neuron disease, making it important to determine which proteins bind VAP. Among other proteins that bind VAP, some contain FFAT-like motifs that are missing one or more of the seven elements. Defining how much variation is tolerated in FFAT-like motifs is a preliminary step prior to the identification of the full range of VAP interactors.
resultsWe used a quantifiable in vivo system that measured ER targeting in a reporter yeast strain that over-expressed VAP to study the effect of substituting different elements of FFAT-like motifs in turn. By defining FFAT-like motifs more widely than before, we found them in novel proteins the functions of which had not previously been directly linked to the ER, including: two PKA anchoring proteins, AKAP220 and AKAP110; a family of plant LTPs; and the glycolipid LTP phosphatidylinositol-four-phosphate adaptor-protein-2 (FAPP-2).
conclusionAll of the seven essential elements of a FFAT motif tolerate variation, and weak targeting to the ER via VAP is still detected if two elements are substituted. In addition to the strong FFAT motifs already known, there are additional proteins with weaker FFAT-like motifs, which might be functionally important VAP interactors.
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