ArticleCell2008
The amyotrophic lateral sclerosis 8 protein VAPB is cleaved, secreted, and acts as a ligand for Eph receptors.
Article in Cell, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 133 papers.
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Who cites it
133 citing papers in PubMed, 239 citations in OpenAlex.
- Protein disulphide isomerase protects against ALS/FTD phenotypes associated with cyclin F in zebrafish and cellular models.Redox report : communications in free radical research · 2026Article
- Fos regulates age-dependent neuroinflammation in a VAPP58S model of amyotrophic lateral sclerosis.Disease models & mechanisms · 2026Article
- Mutual regulation of spermatogenesis-specific Argonaute proteins and Insulin/IGF-1 signaling in aging control.EMBO reports · 2026Article
- Neuronal guidance signaling in neurodegenerative diseases: Key regulators that function at neuron-glia and neuroimmune interfaces.Neural regeneration research · 2026Article
- VAPB is a negative regulator of STING-mediated innate immune signaling.Science advances · 2025Article
- The Vap33 signaling axis precisely coordinates the timing of motoneuron dendritogenesis in neural map development.Nature communications · 2025Article
- Exploring the versatility ofFly · 2025Review
- Mitochondria-Associated Membranes: A Key Point of Neurodegenerative Diseases.CNS neuroscience & therapeutics · 2025Review
- UtilizingJournal of developmental biology · 2025Review
- Pathogenic mechanisms of amyotrophic lateral sclerosis-linked VAPB P56S mutation in the degeneration of corticospinal motor neurons.Ageing and neurodegenerative diseases · 2025Article
- 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
- The Drosophila tumour suppressor Lgl and Vap33 activate the Hippo pathway through a dual mechanism.Journal of cell science · 2024Article
- Article
- RNAi-dependent expression of sperm genes in ADL chemosensory neurons is required for olfactory responses inFrontiers in molecular biosciences · 2024Article
- Neurodegeneration-associated protein VAPB regulates proliferation in medulloblastoma.Scientific reports · 2023Article
- Yeast Models of Amyotrophic Lateral Sclerosis Type 8 Mimic Phenotypes Seen in Mammalian Cells Expressing Mutant VAPBBiomolecules · 2023Article
- Review
- Loss of Activity-Induced Mitochondrial ATP Production Underlies the Synaptic Defects in aThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Caspar, an adapter for VAPB and TER94, modulates the progression of ALS8 by regulating IMD/NFκB-mediated glial inflammation in a Drosophila model of human disease.Human molecular genetics · 2022Article
73 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
VAP proteins (human VAPB/ALS8, Drosophila VAP33, and C. elegans VPR-1) are homologous proteins with an amino-terminal major sperm protein (MSP) domain and a transmembrane domain. The MSP domain is named for its similarity to the C. elegans MSP protein, a sperm-derived hormone that binds to the Eph receptor and induces oocyte maturation. A point mutation (P56S) in the MSP domain of human VAPB is associated with Amyotrophic lateral sclerosis (ALS), but the mechanisms underlying the pathogenesis are poorly understood. Here we show that the MSP domains of VAP proteins are cleaved and secreted ligands for Eph receptors. The P58S mutation in VAP33 leads to a failure to secrete the MSP domain as well as ubiquitination, accumulation of inclusions in the endoplasmic reticulum, and an unfolded protein response. We propose that VAP MSP domains are secreted and act as diffusible hormones for Eph receptors. This work provides insight into mechanisms that may impact the pathogenesis of ALS.
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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.