title: Disturbed vesicular trafficking of membrane proteins in prion disease.
abstract: The pathogenic mechanism of prion diseases remains unknown. We recently reported that prion infection disturbs post-Golgi trafficking of certain types of membrane proteins to the cell surface, resulting in reduced surface expression of membrane proteins and abrogating the signal from the proteins. The surface expression of the membrane proteins was reduced in the brains of mice inoculated with prions, well before abnormal symptoms became evident. Prions or pathogenic prion proteins were mainly detected in endosomal compartments, being particularly abundant in recycling endosomes. Some newly synthesized membrane proteins are delivered to the surface from the Golgi apparatus through recycling endosomes, and some endocytosed membrane proteins are delivered back to the surface through recycling endosomes. These results suggest that prions might cause neuronal dysfunctions and cell loss by disturbing post-Golgi trafficking of membrane proteins via accumulation in recycling endosomes. Interestingly, it was recently shown that delivery of a calcium channel protein to the cell surface was impaired and its function was abrogated in a mouse model of hereditary prion disease. Taken together, these results suggest that impaired delivery of membrane proteins to the cell surface is a common pathogenic event in acquired and hereditary prion diseases.
authors: Division of Molecular Neurobiology; The Institute for Enzyme Research (KOSOKEN); The University of Tokushima; Tokushima, Japan.
authors: Keiji
authors: K
authors: Uchiyama
authors: Animal Research Center; School of Medicine; University of Occupational and Environmental Health; Kitakyushu, Japan.
authors: Hironori
authors: H
authors: Miyata
authors: Division of Molecular Neurobiology; The Institute for Enzyme Research (KOSOKEN); The University of Tokushima; Tokushima, Japan.
authors: Suehiro
authors: S
authors: Sakaguchi
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism / Q000473:pathology; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism / Q000473:pathology*; D006056:Golgi Apparatus / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008565:Membrane Proteins / Q000032:analysis / Q000378:metabolism*; D051379:Mice; D017096:Prion Diseases / Q000378:metabolism* / Q000473:pathology*; D011328:Prions / Q000032:analysis / Q000378:metabolism; D021381:Protein Transport
chemical_list: D008565:Membrane Proteins; D011328:Prions
keywords: Golgi apparatus; Prion; attractin; insulin receptor; neurodegeneration; post-Golgi membrane trafficking; prion disease; prion protein