title: Regulation of the MVB pathway by SCAMP3.
abstract: The biogenesis of multivesicular endosomes and the sorting of activated signaling receptors into multivesicular endosomes depend on soluble protein complexes (ESCRT complexes), which transiently interact with the receptor cargo and the endosomal membrane. Previously, it was shown that the transmembrane protein secretory carrier membrane protein (SCAMP) 3, which is present on endosomes, interacts with ESCRT components. Here, we report that SCAMP3 plays a role in the biogenesis of multivesicular endosomes. We find that SCAMP3 plays a role in EGF receptor sorting into multivesicular endosomes and in the formation of intralumenal vesicles within these endosomes in vitro and thus also controls EGF receptor targeting to lysosomes. We also find that SCAMP3 regulates the EGF-dependent biogenesis of multivesicular endosomes. We conclude that the transmembrane protein SCAMP3 has a positive role in sorting into and budding of intralumenal vesicles and thereby controls the process of multivesicular endosome biogenesis.
authors.affiliation: Biochemistry Department, University of Geneva, 30 quai Ernest Ansermet, Geneva, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Falguières
authors.forename: David
authors.initials: D
authors.lastname: Castle
authors.forename: Jean
authors.initials: J
authors.lastname: Gruenberg
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D006224:Cricetinae; D004591:Electrophoresis, Polyacrylamide Gel; D066246:ErbB Receptors / Q000096:biosynthesis; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism* / Q000648:ultrastructure; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D057146:Multivesicular Bodies / Q000378:metabolism* / Q000648:ultrastructure; D021381:Protein Transport; D034741:RNA, Small Interfering; D033921:Vesicular Transport Proteins / Q000096:biosynthesis
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; D034741:RNA, Small Interfering; C109303:SCAMP3 protein, human; D033921:Vesicular Transport Proteins; D066246:ErbB Receptors