Related Experiment Video
Updated: Nov 26, 2025
Increased Recovery Time and Decreased LPS Administration to Study the Vagus Nerve Stimulation Mechanisms in Limited Inflammatory Responses
Published on: March 29, 2017
Neuroplastin Modulates Anti-inflammatory Effects of MANF
Takuya Yagi1, Rie Asada1, Kohsuke Kanekura2
1Department of Medicine, Division of Endocrinology, Metabolism, and Lipid Research, Washington University School of Medicine, St. Louis, MO 63110, USA.
Abstract:
Endoplasmic reticulum (ER) stress is known to induce pro-inflammatory response and ultimately leads to cell death. Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an ER-localized protein whose expression and secretion is induced by ER stress and a crucial survival factor. However, the underlying mechanism of how MANF exerts its cytoprotective activity remains unclear due to the lack of knowledge of its receptor. Here we show that Neuroplastin (NPTN) is such a receptor for MANF. Biochemical analysis shows the physiological interaction between MANF and NPTN on the cell surface. Binding of MANF to NPTN mitigates the inflammatory response and apoptosis via suppression of NF-kβ signaling. Our results demonstrate that NPTN is a cell surface receptor for MANF, which modulates inflammatory responses and cell death, and that the MANF-NPTN survival signaling described here provides potential therapeutic targets for the treatment of ER stress-related disorders, including diabetes mellitus, neurodegeneration, retinal degeneration, and Wolfram syndrome.
Insights
Mesencephalic astrocyte-derived neurotrophic factor (MANF) binds to its newly identified receptor, Neuroplastin (NPTN), on the cell surface. This interaction suppresses inflammation and apoptosis, offering therapeutic potential for ER stress-related diseases.
Area of Science:
- Cell biology
- Neuroscience
- Molecular biology
Background:
- Endoplasmic reticulum (ER) stress triggers inflammation and cell death.
- Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a survival factor induced by ER stress.
- The receptor and mechanism for MANF's cytoprotective effects were previously unknown.
Purpose of the Study:
- To identify the cell surface receptor for MANF.
- To elucidate the mechanism by which MANF protects cells from ER stress.
- To explore the therapeutic potential of the MANF-receptor interaction.
Main Methods:
- Biochemical analysis to confirm MANF-NPTN interaction.
- Cell surface binding assays.
- Investigation of downstream signaling pathways, including NF-κβ.
Main Results:
- Neuroplastin (NPTN) identified as the cell surface receptor for MANF.
- Demonstrated physiological interaction between MANF and NPTN.
- MANF binding to NPTN suppresses NF-κβ signaling, mitigating inflammation and apoptosis.
Conclusions:
- NPTN is a functional cell surface receptor for MANF.
- The MANF-NPTN axis provides a survival signaling pathway.
- This pathway represents a potential therapeutic target for ER stress-related disorders like diabetes, neurodegeneration, and Wolfram syndrome.
