Alpha-synuclein and polyunsaturated fatty acids promote clathrin-mediated endocytosis and synaptic vesicle recycling |
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Authors: | Ben Gedalya Tziona Loeb Virginie Israeli Eitan Altschuler Yoram Selkoe Dennis J Sharon Ronit |
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Affiliation: | Department of Cellular Biochemistry and Human Genetics, Faculty of Medicine, Hebrew University, Ein-Kerem, Jerusalem 91120, Israel; Department of Pharmacology, School of Pharmacy, Hebrew University, Ein-Kerem, Jerusalem 91120, Israel; Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA |
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Abstract: | α-Synuclein (αS) is an abundant neuronal cytoplasmic protein implicated in Parkinson's disease (PD), but its physiological function remains unknown. Consistent with its having structural motifs shared with class A1 apolipoproteins, αS can reversibly associate with membranes and help regulate membrane fatty acid composition. We previously observed that variations in αS expression level in dopaminergic cultured cells or brains are associated with changes in polyunsaturated fatty acid (PUFA) levels and altered membrane fluidity. We now report that αS acts with PUFAs to enhance the internalization of the membrane-binding dye, FM 1-43. Specifically, αS expression coupled with exposure to physiological levels of certain PUFAs enhanced clathrin-mediated endocytosis in neuronal and non-neuronal cultured cells. Moreover, αS expression and PUFA-enhanced basal and -evoked synaptic vesicle (SV) endocytosis in primary hippocampal cultures of wild type (wt) and genetically depleted αS mouse brains. We suggest that αS and PUFAs normally function in endocytic mechanisms and are specifically involved in SV recycling upon neuronal stimulation. |
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Keywords: | α-synuclein clathrin-mediated endocytosis membrane fluidity membrane trafficking Parkinson's disease polyunsaturated fatty acids synaptic vesicle recycling |
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