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The novel lipid raft adaptor p18 controls endosome dynamics by anchoring the MEK-ERK pathway to late endosomes.

ABSTRACT: 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.

SUBMITTER: Nada S

PROVIDER: S-EPMC2657578 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature

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The novel lipid raft adaptor p18 controls endosome dynamics by anchoring the MEK-ERK pathway to late endosomes.

Nada Shigeyki S Hondo Akihiro A Kasai Atsuko A Koike Masato M Saito Kazunobu K Uchiyama Yasuo Y Okada Masato M

The EMBO journal 20090129 5

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 endo ...[more]

PMID: 19177150

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Dataset Information

The novel lipid raft adaptor p18 controls endosome dynamics by anchoring the MEK-ERK pathway to late endosomes.

Publications

The novel lipid raft adaptor p18 controls endosome dynamics by anchoring the MEK-ERK pathway to late endosomes.

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