The novel lipid raft adaptor p18 controls endosome dynamics by anchoring the MEK–ERK pathway to late endosomes
Open accessAbstract
The regulation of endosome dynamics is crucial for fundamental cellular functions, such as nutrient intake/digestion, membrane protein cycling, cell migration and intracellular signalling. Here, we show that a novel lipid raft adaptor protein, p18, is involved in controlling endosome dynamics by anchoring the MEK1-ERK pathway to late endosomes. p18 is anchored to lipid rafts of late endosomes through its N-terminal unique region. p18(-/-) mice are embryonic lethal and have severe defects in endosome/lysosome organization and membrane protein transport in the visceral endoderm. p18(-/-) cells exhibit apparent defects in endosome dynamics through perinuclear compartment, such as aberrant distribution and/or processing of lysosomes and impaired cycling of Rab11-positive recycling endosomes. p18 specifically binds to the p14-MP1 complex, a scaffold for MEK1. Loss of p18 function excludes the p14-MP1 complex from late endosomes, resulting in a downregulation of the MEK-ERK activity. These results indicate that the lipid raft adaptor p18 is essential for anchoring the MEK-ERK pathway to late endosomes, and shed new light on a role of endosomal MEK-ERK pathway in controlling endosome dynamics.
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p18 is the key determinant of lysosome localization by virtue of lipid modifications within its N-terminal region.
“The protein p18 was shown to be the key determinant of lysosome localization by virtue of lipid modifications within its N-terminal region (Bar-Peled et al., 2012; Nada et al., 2009).”
From Signal integration in the (m)TORC1 growth pathway (2018) · cites this paper as Nada et al., 2009
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- Authors
- Nada, S., Hondo, A., Kasai, A., Koike, M., Saito, K., Uchiyama, Y., & Okada, M.
- Affiliations
- Research Institute for Microbial Diseases, The University of Osaka (JP)
- Juntendo University (JP)
- Corresponding author
- Okada, Masato
- Venue
- The EMBO Journal
- Published
- 2009-01-29
- Volume
- 28
- Issue
- 5
- Pages
- 477-489
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC2657578
- OpenAlex
- W2084712051
- Cited by
- 341
- References
- 63
- Citations by year
- 2026: 13 · 2025: 8 · 2024: 9 · 2023: 20 · 2022: 20 · 2021: 22 · 2020: 26 · 2019: 20 · 2018: 24 · 2017: 23 · 2016: 20 · 2015: 22 · 2014: 16 · 2013: 21 · 2012: 35
- FWCI
- 11.42
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The EMBO Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Yasuda Memorial Medical Foundation
- Research Institute for Microbial Diseases, Osaka University
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- p18, lipid rafts, late endosomes, MEK/ERK signaling, MEK1, recycling endosomes, membrane protein transport, visceral endoderm, embryonic lethality, Rab11
- MeSH terms
- Amino Acid Sequence, Animals, Cells, Cultured, Endocytosis, Endoderm, Epidermal Growth Factor, Lysosomes, Molecular Sequence Data, Protein Binding, Proteins, Endosomes, Signal Transduction, Mice, Knockout, Membrane Microdomains, Extracellular Signal-Regulated MAP Kinases, MAP Kinase Kinase 1, Adaptor Proteins, Signal Transducing, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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