ArticlePLoS genetics2013
VAPB/ALS8 MSP ligands regulate striated muscle energy metabolism critical for adult survival in caenorhabditis elegans.
Article in PLoS genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.
- Identification of let-7f and miR-338 as plasma-based biomarkers for sporadic amyotrophic lateral sclerosis using meta-analysis and empirical validation.Scientific reports · 2022Pooled it
- Mutual regulation of spermatogenesis-specific Argonaute proteins and Insulin/IGF-1 signaling in aging control.EMBO reports · 2026Article
- 6-PPD induces mitochondrial dysfunction and reduces healthspan and lifespan through SKN-1 in Caenorhabditis elegans.Journal of hazardous materials · 2025Article
- Microglial lipid droplets as therapeutic targets in age-related neurodegenerative diseases.npj aging · 2025Review
- Deciphering distinct genetic risk factors for FTLD-TDP pathological subtypes via whole-genome sequencing.Nature communications · 2025Article
- Amyotrophic Lateral Sclerosis (ALS): An Overview of Genetic and Metabolic Signaling Mechanisms.CNS & neurological disorders drug targets · 2025Review
- Pathogenic mechanisms of amyotrophic lateral sclerosis-linked VAPB P56S mutation in the degeneration of corticospinal motor neurons.Ageing and neurodegenerative diseases · 2025Article
- Muscle Involvement in Amyotrophic Lateral Sclerosis: Understanding the Pathogenesis and Advancing Therapeutics.Biomolecules · 2023Review
- VAPB-mediated ER-targeting stabilizes IRS-1 signalosomes to regulate insulin/IGF signaling.Cell discovery · 2023Article
- Review
- Overexpression of mTOR in Leukocytes from ALS8 Patients.Current neuropharmacology · 2023Article
- Simple models to understand complex disease: 10 years of progress fromFrontiers in neuroscience · 2023Review
- Review
- VAP Proteins - From Organelle Tethers to Pathogenic Host Interactors and Their Role in Neuronal Disease.Frontiers in cell and developmental biology · 2022Review
- The type II integral ER membrane protein VAP-B homolog in C. elegans is cleaved to release the N-terminal MSP domain to signal non-cell-autonomously.Developmental biology · 2021Article
- Patient-Specific Cells for Modeling and Decoding Amyotrophic Lateral Sclerosis: Advances and Challenges.Stem cell reviews and reports · 2020Review
- Emerging Links between Lipid Droplets and Motor Neuron Diseases.Developmental cell · 2018Article
- The secreted MSP domain ofDevelopment (Cambridge, England) · 2017Article
- TheDevelopment (Cambridge, England) · 2017Article
- Comparison of independent screens on differentially vulnerable motor neurons reveals alpha-synuclein as a common modifier in motor neuron diseases.PLoS genetics · 2017Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
Mutations in VAPB/ALS8 are associated with amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA), two motor neuron diseases that often include alterations in energy metabolism. We have shown that C. elegans and Drosophila neurons secrete a cleavage product of VAPB, the N-terminal major sperm protein domain (vMSP). Secreted vMSPs signal through Roundabout and Lar-like receptors expressed on striated muscle. The muscle signaling pathway localizes mitochondria to myofilaments, alters their fission/fusion balance, and promotes energy production. Here, we show that neuronal loss of the C. elegans VAPB homolog triggers metabolic alterations that appear to compensate for muscle mitochondrial dysfunction. When vMSP levels drop, cytoskeletal or mitochondrial abnormalities in muscle induce elevated DAF-16, the Forkhead Box O (FoxO) homolog, transcription factor activity. DAF-16 promotes muscle triacylglycerol accumulation, increases ATP levels in adults, and extends lifespan, despite reduced muscle mitochondria electron transport chain activity. Finally, Vapb knock-out mice exhibit abnormal muscular triacylglycerol levels and FoxO target gene transcriptional responses to fasting and refeeding. Our data indicate that impaired vMSP signaling to striated muscle alters FoxO activity, which affects energy metabolism. Abnormalities in energy metabolism of ALS patients may thus constitute a compensatory mechanism counterbalancing skeletal muscle mitochondrial dysfunction.
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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.