ArticleNature communications2019
MANF antagonizes nucleotide exchange by the endoplasmic reticulum chaperone BiP.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 1 of them a synthesis that pooled it.
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Who cites it
59 citing papers in PubMed, 1 synthesis or guideline pooled it, 111 citations in OpenAlex.
- Neuroprotective and reparative effects of endoplasmic reticulum luminal proteins - mesencephalic astrocyte-derived neurotrophic factor and cerebral dopamine neurotrophic factor.Croatian medical journal · 2019Pooled it
- Structure and mechanism of the HSV-1 origin-binding protein UL9.Journal of virology · 2026Article
- MANF in the lateral septum dynamically regulates endoplasmic reticulum function in chronic stress response.Translational psychiatry · 2026Article
- Spatial transcriptomics analysis uncovers ER stress in MANF-deficient Purkinje cells underlying alcohol-induced cerebellar neurodegeneration in mice.Acta neuropathologica communications · 2025Article
- Diabetes mellitus and the key role of endoplasmic reticulum stress in pancreatic β cells.Nature reviews. Endocrinology · 2025Review
- A multichaperone condensate enhances protein folding in the endoplasmic reticulum.Nature cell biology · 2025Article
- Cerebral Dopamine Neurotrophic Factor (CDNF) Acts as a Trophic Factor Promoting Neuritogenesis in the Dorsal Root Ganglia (DRG) Neurons Through Activation of the PI3K Signaling Pathway.Journal of neurochemistry · 2025Article
- Mechanism of ATP hydrolysis in the Hsp70 BiP nucleotide-binding domain.Nature communications · 2025Article
- Bridging systemic metabolic dysfunction and Alzheimer's disease: the liver interface.Molecular neurodegeneration · 2025Review
- The structural and functional dynamics of BiP and Grp94: opportunities for therapeutic discovery.Trends in pharmacological sciences · 2025Review
- Paternal Obesity-Induced H3K27me3 Elevation Leads to MANF-Mediated Transgenerational Metabolic Dysfunction in Female Offspring.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Mesencephalic Astrocyte-Derived Neurotrophic Factor (MANF) Mitigates Neuroinflammation and Cognitive Impairment by Modulating Glial Activation in Sepsis-Associated Encephalopathy.Neurochemical research · 2024Article
- Unlocking the promise of MANF in diseases: Mechanistic insights and therapeutic potentials.Molecular biology reports · 2024Review
- Targeting Rap1b signaling cascades with CDNF: Mitigating platelet activation, plasma oxylipins and reperfusion injury in stroke.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Mechanistic role of mesencephalic astrocyte-derived neurotrophic factor in myocardial ischemia/reperfusion injury.Molecular medicine (Cambridge, Mass.) · 2024Article
- Increased expression of mesencephalic astrocyte-derived neurotrophic factor (MANF) contributes to synapse loss in Alzheimer's disease.Molecular neurodegeneration · 2024Article
- Structural basis of CDNF interaction with the UPR regulator GRP78.Nature communications · 2024Article
- Dual role of neuroplastin in pancreatic β cells: Regulating insulin secretion and promoting islet inflammation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The Essential Functions of Molecular Chaperones and Folding Enzymes in Maintaining Endoplasmic Reticulum Homeostasis.Journal of molecular biology · 2024Review
- Ferroptosis and endoplasmic reticulum stress in ischemic stroke.Neural regeneration research · 2024Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Despite its known role as a secreted neuroprotectant, much of the mesencephalic astrocyte-derived neurotrophic factor (MANF) is retained in the endoplasmic reticulum (ER) of producer cells. There, by unknown mechanisms, MANF plays a role in protein folding homeostasis in complex with the ER-localized Hsp70 chaperone BiP. Here we report that the SAF-A/B, Acinus, and PIAS (SAP) domain of MANF selectively associates with the nucleotide binding domain (NBD) of ADP-bound BiP. In crystal structures the SAP domain engages the cleft between NBD subdomains Ia and IIa, stabilizing the ADP-bound conformation and clashing with the interdomain linker that occupies this site in ATP-bound BiP. MANF inhibits both ADP release from BiP and ATP binding to BiP, and thereby client release. Cells lacking MANF have fewer ER stress-induced BiP-containing high molecular weight complexes. These findings suggest that MANF contributes to protein folding homeostasis as a nucleotide exchange inhibitor that stabilizes certain BiP-client complexes.
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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.