title: Protein oligomerization modulates raft partitioning and apical sorting of GPI-anchored proteins.
abstract: An essential but insufficient step for apical sorting of glycosylphosphatidylinositol (GPI)-anchored proteins (GPI-APs) in epithelial cells is their association with detergent-resistant microdomains (DRMs) or rafts. In this paper, we show that in MDCK cells both apical and basolateral GPI-APs associate with DRMs during their biosynthesis. However, only apical and not basolateral GPI-APs are able to oligomerize into high molecular weight complexes. Protein oligomerization begins in the medial Golgi, concomitantly with DRM association, and is dependent on protein-protein interactions. Impairment of oligomerization leads to protein missorting. We propose that oligomerization stabilizes GPI-APs into rafts and that this additional step is required for apical sorting of GPI-APs. Two alternative apical sorting models are presented.
authors.affiliation: Dipartimento di Biologia e Patologia Cellulare e Molecolare, Centro di Endocrinologia ed Oncologia Sperimentale, CNR, Università degli Studi di Napoli Federico II, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Paladino
authors.forename: Daniela
authors.initials: D
authors.lastname: Sarnataro
authors.forename: Rudolf
authors.initials: R
authors.lastname: Pillich
authors.forename: Simona
authors.initials: S
authors.lastname: Tivodar
authors.forename: Lucio
authors.initials: L
authors.lastname: Nitsch
authors.forename: Chiara
authors.initials: C
authors.lastname: Zurzolo
mesh_terms: D000818:Animals; D002460:Cell Line; D016764:Cell Polarity / Q000502:physiology*; D002784:Cholesterol / Q000378:metabolism; D004285:Dogs; D004847:Epithelial Cells / Q000378:metabolism*; D017261:Glycosylphosphatidylinositols / Q000096:biosynthesis*; D006056:Golgi Apparatus / Q000378:metabolism; D046911:Macromolecular Substances / Q000378:metabolism; D021962:Membrane Microdomains / Q000378:metabolism*; D008954:Models, Biological; D011108:Polymers / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology
chemical_list: D017261:Glycosylphosphatidylinositols; D046911:Macromolecular Substances; D011108:Polymers; D002784:Cholesterol