title: Erlin-1 and erlin-2 are novel members of the prohibitin family of proteins that define lipid-raft-like domains of the ER.
abstract: Our laboratory was interested in characterizing the molecular composition of non-caveolar lipid rafts. Thus, we generated monoclonal antibodies to lipid raft proteins of human myelomonocytic cells. Two of these proteins, KE04p and C8orf2, were found to be highly enriched in the detergent-insoluble, buoyant fraction of sucrose gradients in a cholesterol-dependent manner. They contain an evolutionarily conserved domain placing them in the prohibitin family of proteins. In contrast to other family members, these two proteins localized to the ER. Furthermore, the extreme N-termini of KE04p and C8orf2 were found to be sufficient for heterologous targeting of GFP to the ER in the absence of classical ER retrieval motifs. We also demonstrate that all prohibitin family members rely on sequences in their extreme N-termini for their distinctive subcellular distributions including the mitochondria, plasma membrane and Golgi vesicles. Owing to their subcellular localization and their presence in lipid rafts, we have named KE04p and C8orf2, ER lipid raft protein (erlin)-1 and erlin-2, respectively. Interestingly, the ER contains relatively low levels of cholesterol and sphingolipids compared with other organelles. Thus, our data support the existence of lipid-raft-like domains within the membranes of the ER.
authors.affiliation: Southern Alberta Cancer Research Institute, Departments of Oncology and Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta, T2N 4N1, Canada.
authors.forename: Duncan T
authors.initials: DT
authors.lastname: Browman
authors.forename: Mary E
authors.initials: ME
authors.lastname: Resek
authors.forename: Laura D
authors.initials: LD
authors.lastname: Zajchowski
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Robbins
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D021962:Membrane Microdomains / Q000737:chemistry / Q000378:metabolism*; D008565:Membrane Proteins / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009000:Monocytes / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D010802:Phylogeny; D000091402:Prohibitins; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D013347:Subcellular Fractions / Q000737:chemistry / Q000378:metabolism
chemical_list: C418605:ERLIN1 protein, human; C121703:ERLIN2 protein, human; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D000091402:Prohibitins; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; C036860:STOM protein, human; C106354:flotillins; D002784:Cholesterol