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ARMH3 acts as a central scaffold at the Golgi/TGN through interactions with Arl5, GBF1, and PI4KB.

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Title: ARMH3 acts as a central scaffold at the Golgi/TGN through interactions with Arl5, GBF1, and PI4KB.
Authors: Scott MK; School of Molecular Life Sciences, University of Victoria, Victoria, British Columbia, Canada., Klynsoon GCT; School of Molecular Life Sciences, University of Victoria, Victoria, British Columbia, Canada., Walsh EE; School of Molecular Life Sciences, University of Victoria, Victoria, British Columbia, Canada., Suresh S; School of Molecular Life Sciences, University of Victoria, Victoria, British Columbia, Canada., Nyvall HG; Department of Biochemistry and Molecular Biology, The University of British Columbia, Vancouver, British Columbia, Canada., Burke JE; School of Molecular Life Sciences, University of Victoria, Victoria, British Columbia, Canada; Department of Biochemistry and Molecular Biology, The University of British Columbia, Vancouver, British Columbia, Canada; University of Victoria Genome BC Proteomics Centre, Victoria, British Columbia, Canada. Electronic address: jeburke@uvic.ca.
Source: The Journal of biological chemistry [J Biol Chem] 2026 Aug; Vol. 302 (8), pp. 113307. Date of Electronic Publication: 2026 Jun 29.
Publication Type: Journal Article; Research Support, Non-U.S. Gov't
Language: English
Journal Info: 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
MeSH Terms: Guanine Nucleotide Exchange Factors*/metabolism , Guanine Nucleotide Exchange Factors*/chemistry , Golgi Apparatus*/metabolism , trans-Golgi Network*/metabolism , ADP-Ribosylation Factors*/metabolism , ADP-Ribosylation Factors*/chemistry , Phosphotransferases (Alcohol Group Acceptor)*/metabolism , Phosphotransferases (Alcohol Group Acceptor)*/chemistry , 1-Phosphatidylinositol 4-Kinase*/metabolism , 1-Phosphatidylinositol 4-Kinase*/chemistry, Humans ; Protein Binding
Abstract: The armadillo repeat protein ARMH3 regulates the activity and localization of the Golgi resident lipid kinase phosphatidylinositol 4 kinase IIIβ (PI4KB) and the Golgi-specific brefeldin A-resistance guanine nucleotide exchange factor 1 (GBF1) that activates Arf1. ARMH3 localizes to the trans-Golgi network (TGN) via the GTPase Arl5. We used hydrogen deuterium exchange mass spectrometry (HDX-MS) and AI-enabled modeling to define the interfaces of ARMH3 with its binding partners Arl5, PI4KB, and GBF1. The ARMH3-Arl5 interface was determined to consist of regions near the N and C termini of ARMH3, with Arl5 binding causing allosteric conformational changes in ARMH3 located at a shared PI4KB/GBF1 interface. ARMH3 binds to PI4KB and GBF1 at this shared competitive interface, with GBF1 binding to ARMH3 through a disordered loop we have named the ARMH3-binding region (ABR). Both GBF1 and PI4KB can form ternary complexes with ARMH3-Arl5. The ARMH3 interfaces in PI4KB and GBF1 contain phosphosites, with the phosphomimetic mutation of GBF1 blocking complex formation. These findings provide new insights into the role of ARMH3 as a master coordinator of GTPase and phosphoinositide signaling at the Golgi/TGN.
(Copyright © 2026 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.
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Contributed Indexing: Keywords: ARMH3; Arl5; GBF1; GTPases; Golgi/TGN; PI4KB; hydrogen–deuterium exchange mass spectrometry
Substance Nomenclature: 0 (Guanine Nucleotide Exchange Factors)
0 (GBF1 protein, human)
EC 2.7.1.67 (PI4KB protein, human)
EC 3.6.5.2 (ADP-Ribosylation Factors)
EC 2.7.1.- (Phosphotransferases (Alcohol Group Acceptor))
EC 2.7.1.67 (1-Phosphatidylinositol 4-Kinase)
Entry Date(s): Date Created: 20260629 Date Completed: 20260820 Latest Revision: 20260923
Update Code: 20260923
PubMed Central ID: PMC13427656
DOI: 10.1016/j.jbc.2026.113307
PMID: 42372921
Database: MEDLINE
Description
ISSN:1083-351X
DOI:10.1016/j.jbc.2026.113307