Ganglioside-induced amyloid formation by human islet amyloid polypeptide in lipid rafts.
Human islet amyloid polypeptide (hIAPP) is the primary component of the amyloid deposits found in the pancreatic islets of patients with type 2 diabetes mellitus. However, it is unknown how amyloid fibrils are formed in vivo. In this study, we demonstrate that gangliosides play an essential role in the formation of amyloid deposits by hIAPP on plasma membranes. Amyloid fibrils accumulated in ganglioside- and cholesterol-rich microscopic domains ('lipid rafts'). The depletion of gangliosides or cholesterol significantly reduced the amount of amyloid deposited. These results clearly showed that the formation of amyloid fibrils was mediated by gangliosides in lipid rafts.
Wakabayashi
Masaki
M
Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan.
Matsuzaki
Katsumi
K
D000682:Amyloid / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D002784:Cholesterol / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000473:pathology; D005732:Gangliosides / Q000378:metabolism*; D006801:Humans; D058228:Islet Amyloid Polypeptide; D007515:Islets of Langerhans / Q000737:chemistry / Q000473:pathology; D021962:Membrane Microdomains / Q000737:chemistry / Q000378:metabolism*; D016716:PC12 Cells; D051381:Rats
D000682:Amyloid; D005732:Gangliosides; D058228:Islet Amyloid Polypeptide; D002784:Cholesterol