AMER1 regulates the distribution of the tumor suppressor APC between microtubules and the plasma membrane
Abstract
APC is a multifunctional tumor suppressor protein that negatively controls Wnt signaling, but also regulates cell adhesion and migration by interacting with the plasma membrane and the microtubule cytoskeleton. Although the molecular basis for the microtubule association of APC is well understood, molecular mechanisms that underlie its plasma membrane localization have remained elusive. We show here that APC is recruited to the plasma membrane by binding to APC membrane recruitment 1 (AMER1), a novel membrane-associated protein that interacts with the ARM repeat domain of APC. The N-terminus of AMER1 contains two distinct phosphatidylinositol(4,5)-bisphosphate [PtdIns(4,5)P2]-binding domains, which mediate its localization to the plasma membrane. Overexpression of AMER1 increases APC levels and redirects APC from microtubule ends to the plasma membrane of epithelial cells. Conversely, siRNA-mediated knockdown of AMER1 reduces the overall levels of APC, promotes its association with microtubule ends in cellular protrusions and disturbs intercellular junctions. These data indicate that AMER1 controls the subcellular distribution of APC between membrane- and microtubule-associated pools, and might thereby regulate APC-dependent cellular morphogenesis, cell migration and cell-cell adhesion.
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Additional genes of interest that had comutation interactions with KRAS G12D include increased comutation with AMER1.
“These include increased comutation with AMER1, a negative regulator of Wnt signaling53,54.”
From The origins and genetic interactions of KRAS mutations are allele- and tissue-specific (2021) · cites this paper as [53]
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- Authors
- Grohmann, A., Tanneberger, K., Alzner, A., Schneikert, J., & Behrens, J.
- Affiliations
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- Nikolaus-Fiebiger-Center for Molecular Medicine, University Erlangen-Nuremberg, Glückstr. 6, 91054 Erlangen, Germany
- ORCID
- Schneikert, Jean
- Venue
- Journal of Cell Science
- Publisher
- The Company of Biologists
- Published
- 2007-11-01
- Volume
- 120
- Issue
- 21
- Pages
- 3738-3747
- ISSN
- 0021-9533 (ISSN-L)
- 1477-9137
- OpenAlex
- W2108699597
- Cited by
- 85
- References
- 43
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 6 · 2023: 1 · 2022: 3 · 2021: 4 · 2020: 3 · 2019: 6 · 2018: 3 · 2017: 4 · 2015: 4 · 2014: 3 · 2013: 6 · 2012: 8
- FWCI
- 2.25
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Cell Science (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hippo pathway signaling and YAP/TAZ
- Keywords
- AMER1, APC tumor suppressor, microtubules, plasma membrane localization, subcellular localization, epithelial cells, cell migration, cell-cell adhesion, intercellular junctions, Wnt signaling, cell protrusions
- MeSH terms
- Amino Acid Sequence, Animals, Cell Membrane, Humans, Membrane Proteins, Microtubules, Molecular Sequence Data, Sequence Alignment, Two-Hybrid System Techniques, Tumor Suppressor Proteins, Adenomatous Polyposis Coli Protein, Cell Line, Tumor, Adaptor Proteins, Signal Transducing
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