title: Stability of the endosomal scaffold protein LAMTOR3 depends on heterodimer assembly and proteasomal degradation.
abstract: LAMTOR3 (MP1) and LAMTOR2 (p14) form a heterodimer as part of the larger Ragulator complex that is required for MAPK and mTOR1 signaling from late endosomes/lysosomes. Here, we show that loss of LAMTOR2 (p14) results in an unstable cytosolic monomeric pool of LAMTOR3 (MP1). Monomeric cytoplasmic LAMTOR3 is rapidly degraded in a proteasome-dependent but lysosome-independent manner. Mutational analyses indicated that the turnover of the protein is dependent on ubiquitination of several lysine residues. Similarly, other Ragulator subunits, LAMTOR1 (p18), LAMTOR4 (c7orf59), and LAMTOR5 (HBXIP), are degraded as well upon the loss of LAMTOR2. Thus the assembly of the Ragulator complex is monitored by cellular quality control systems, most likely to prevent aberrant signaling at the convergence of mTOR and MAPK caused by a defective Ragulator complex.
authors: Biocenter, Division of Cell Biology, Innsbruck Medical University, A-6020 Innsbruck, Austria.
authors: Mariana E G
authors: ME
authors: de Araújo
authors: Taras
authors: T
authors: Stasyk
authors: Nicole
authors: N
authors: Taub
authors: Hannes L
authors: HL
authors: Ebner
authors: Beatrix
authors: B
authors: Fürst
authors: Przemyslaw
authors: P
authors: Filipek
authors: Sabine R
authors: SR
authors: Weys
authors: Michael W
authors: MW
authors: Hess
authors: Herbert
authors: H
authors: Lindner
authors: Leopold
authors: L
authors: Kremser
authors: Lukas A
authors: LA
authors: Huber
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000166:cytology; D011992:Endosomes / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D055503:Protein Multimerization; D055550:Protein Stability; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D059748:Proteolysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C426009:LAMTOR2 protein, mouse; C114559:Lamtor3 protein, mouse; D011506:Proteins; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex
keywords: LAMTOR1 (p18); LAMTOR2 (p14); LAMTOR3 (MP1); LAMTOR4 (c7orf59); MAP Kinases (MAPKs); Protein Degradation; Scaffold Proteins; Signal Transduction; and LAMTOR5 (HBXIP); mTOR
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