Academic Journal
GRIA1 regulates TGN export and secretion of Sonic hedgehog.
| Τίτλος: | GRIA1 regulates TGN export and secretion of Sonic hedgehog. |
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| Συγγραφείς: | Tang X; Anhui Provincial Key Laboratory of Molecular Enzymology and Mechanism of Major Metabolic Diseases, College of Life Sciences, Anhui Normal University, Wuhu, China. Electronic address: tangxiao@ahnu.edu.cn., Tian Y; Division of Life Science, The Hong Kong University of Science and Technology, Hong Kong, China., Wang Q; Anhui Provincial Key Laboratory of Molecular Enzymology and Mechanism of Major Metabolic Diseases, College of Life Sciences, Anhui Normal University, Wuhu, China., Song Z; Anhui Provincial Key Laboratory of Molecular Enzymology and Mechanism of Major Metabolic Diseases, College of Life Sciences, Anhui Normal University, Wuhu, China., Zhao X; Anhui Provincial Key Laboratory of Molecular Enzymology and Mechanism of Major Metabolic Diseases, College of Life Sciences, Anhui Normal University, Wuhu, China., Guo Y; Division of Life Science, The Hong Kong University of Science and Technology, Hong Kong, China. Electronic address: guoyusong@ust.hk. |
| Πηγή: | The Journal of biological chemistry [J Biol Chem] 2026 Feb; Vol. 302 (2), pp. 111084. Date of Electronic Publication: 2025 Dec 22. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Country of Publication: United States NLM ID: 2985121R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1083-351X (Electronic) Linking ISSN: 00219258 NLM ISO Abbreviation: J Biol Chem Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2021- : [New York, NY] : Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Original Publication: Baltimore, MD : American Society for Biochemistry and Molecular Biology |
| Ιατρικοί όροι (MeSH): | Hedgehog Proteins*/metabolism , Hedgehog Proteins*/genetics , trans-Golgi Network*/metabolism , trans-Golgi Network*/genetics , Receptors, AMPA*/metabolism , Receptors, AMPA*/genetics, Endoplasmic Reticulum/metabolism ; Golgi Apparatus/metabolism ; Humans ; Protein Transport ; Animals ; Mice ; HEK293 Cells ; HeLa Cells |
| Περίληψη: | Sonic hedgehog (Shh) signaling orchestrates diverse developmental processes in metazoans and is implicated in numerous human diseases. While downstream signaling in recipient cells have been extensively characterized, the mechanisms governing secretion of newly synthesized Shh from producer cells remain less well understood. Building on our previous identification of a Surfeit locus protein 4 (SURF4)-to-proteoglycan (PG) relay mechanism that mediates endoplasmic reticulum (ER)-to-Golgi transport of the N-terminal Shh fragment (ShhN), we investigated ShhN export from the trans-Golgi network (TGN). We show that ShhN exits the TGN via a clathrin-dependent secretory pathway. Mechanistic analyses identify the transmembrane protein glutamate receptor 1 (GRIA1) as a key mediator: GRIA1 associates with ShhN in Golgi-derived vesicles, physically interacts with ShhN, colocalizes with ShhN after TGN exit, and is required for efficient TGN export and secretion of ShhN. Notably, the Cardin-Weintraub (CW) motif on ShhN, previously shown to engage SURF4 for ER-to-Golgi trafficking, is also essential for TGN export, and PGs are critical for the GRIA1-ShhN interaction. Furthermore, GRIA1 regulates intracellular trafficking of endogenous full length Shh and modulates Shh pathway activity in Neuro-2a (N2A) cells. Together, these findings identify GRIA1 as an important regulator of Shh TGN export and advance our understanding of the molecular mechanisms that control Shh secretion. (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.) |
| Competing Interests: | Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article. |
| Contributed Indexing: | Keywords: GRIA1; Sonic hedgehog; TGN export; clathrin; protein secretion |
| Substance Nomenclature: | 0 (Hedgehog Proteins) 0 (Receptors, AMPA) 0 (SHH protein, human) |
| Entry Date(s): | Date Created: 20251224 Date Completed: 20260305 Latest Revision: 20260305 |
| Update Code: | 20260306 |
| PubMed Central ID: | PMC12858347 |
| DOI: | 10.1016/j.jbc.2025.111084 |
| PMID: | 41443413 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1083-351X |
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| DOI: | 10.1016/j.jbc.2025.111084 |