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| Main Authors: | , , , , , , |
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| Format: | Artículo científico |
| Language: | en |
| Published: |
Zoological research
2025
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| Subjects: | |
| Online Access: | https://pubmed.ncbi.nlm.nih.gov/41017400/ |
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Table of Contents:
- LEAP2 triggers retromer-mediated membrane trafficking of MOSPD2 to promote chemotaxis in teleost monocytes/macrophages. Zhu, Ting-Fang Zhao, Zi-Yue Fei, Chen-Jie Shen, Shi-Chang Shao, Jian-Zhong Nie, Li Chen, Jiong Animals Chemotaxis Macrophages Monocytes Fish Proteins Protein Transport Antimicrobial Cationic Peptides Gene Expression Regulation Liver-expressed antimicrobial peptide 2 (LEAP2) is a key regulator of innate immune defense in teleosts, yet the molecular basis of its chemotactic function remains largely unidentified. MOSPD2 ( MOSPD2) was previously identified as a candidate receptor for LEAP2 in monocytes/macrophages (MO/MΦ). In the present study, LEAP2 stimulation was found to trigger a retromer-dependent intracellular trafficking program essential for MOSPD2-mediated chemotaxis. Exposure to LEAP2 significantly enhanced MO/MΦ migration and promoted the accumulation of MOSPD2 at the plasma membrane. Subcellular fractionation and immunofluorescence analyses revealed that MOSPD2 translocated from the endoplasmic reticulum (ER) to early endosomes upon LEAP2 stimulation, followed by redistribution to the cell surface. Blockade of ER export or knockdown of core retromer subunits ( VPS35, VPS26, or VPS29) abolished membrane localization and attenuated LEAP2-induced migration. Co-immunoprecipitation combined with mass spectrometry confirmed direct binding between MOSPD2 and VPS35, while domain-mapping indicated that this interaction was not exclusively dependent on MSP or CRAL-TRIO domains. Depletion of individual retromer components led to retention of MOSPD2 in early endosomes, establishing the necessity of the retromer complex for receptor recycling. Functionally, disruption of this complex eliminated the pro-migratory activity of LEAP2 on MO/MΦ. These findings identify the retromer complex as a critical regulator of MOSPD2 trafficking and uncover a previously unrecognized mechanism through which LEAP2 promotes MO/MΦ migration in teleosts.