Interactions of Synphilin-1 with phospholipids and lipid membranes.
Synphilin-1 is an alpha-synuclein binding protein that is involved in the pathogenesis of Parkinson's disease. The present study investigated the phospholipid-binding capacity of Synphilin-1. The C-terminus of Synphilin-1 was found to selectively bind to acidic phospholipids, including phosphatidic acid, phosphatidylserine, and phosphatidylglycerol, but not to naturally charged phospholipids. Synphilin-1 was targeted to cytoplasmic lipid droplets in mammalian cells. The amino acid sequence 610-640 was found to represent the primary determinant site for phospholipid binding. Moreover, the R621C mutation identified in Parkinson's disease abolished Synphilin-1 association with lipid droplets. The lipophilicity of Synphilin-1 might prove relevant to its physiologic function.
Takahashi
Tetsuya
T
Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical Sciences, 1-2-3 Kasumi, Hiroshima 734-8551, Japan.
Yamashita
Hiroshi
H
Nagano
Yoshito
Y
Nakamura
Takeshi
T
Kohriyama
Tatsuo
T
Matsumoto
Masayasu
M
D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D002352:Carrier Proteins / Q000032:analysis / Q000737:chemistry* / Q000378:metabolism*; D002522:Chlorocebus aethiops; D006801:Humans; D008055:Lipids / Q000032:analysis; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000737:chemistry* / Q000378:metabolism*; D010712:Phosphatidic Acids / Q000378:metabolism; D010718:Phosphatidylserines / Q000378:metabolism; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism*
D002352:Carrier Proteins; D008055:Lipids; D009419:Nerve Tissue Proteins; D010712:Phosphatidic Acids; D010718:Phosphatidylserines; D010743:Phospholipids; C118958:SNCAIP protein, human