Alpha-synuclein and polyunsaturated fatty acids promote clathrin-mediated endocytosis and synaptic vesicle recycling.
Alpha-synuclein (alphaS) 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, alphaS can reversibly associate with membranes and help regulate membrane fatty acid composition. We previously observed that variations in alphaS 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 alphaS acts with PUFAs to enhance the internalization of the membrane-binding dye, FM 1-43. Specifically, alphaS expression coupled with exposure to physiological levels of certain PUFAs enhanced clathrin-mediated endocytosis in neuronal and non-neuronal cultured cells. Moreover, alphaS expression and PUFA-enhanced basal and -evoked synaptic vesicle (SV) endocytosis in primary hippocampal cultures of wild type (wt) and genetically depleted alphaS mouse brains. We suggest that alphaS and PUFAs normally function in endocytic mechanisms and are specifically involved in SV recycling upon neuronal stimulation.
Ben Gedalya
Tziona
T
Department of Cellular Biochemistry and Human Genetics, Faculty of Medicine, Hebrew University, Ein-Kerem, Jerusalem 91120, Israel.
Loeb
Virginie
V
Israeli
Eitan
E
Altschuler
Yoram
Y
Selkoe
Dennis J
DJ
Sharon
Ronit
R
D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002966:Clathrin / Q000378:metabolism*; D004705:Endocytosis; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism; D055503:Protein Multimerization; D021381:Protein Transport; D011990:Receptors, Transferrin / Q000378:metabolism; D012995:Solubility; D013572:Synaptic Vesicles / Q000378:metabolism*; D046509:Tissue Culture Techniques; D014168:Transferrin / Q000378:metabolism; D051844:alpha-Synuclein / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
D002966:Clathrin; D005231:Fatty Acids, Unsaturated; D011990:Receptors, Transferrin; D014168:Transferrin; D051844:alpha-Synuclein