TY - JOUR
T1 - α-Synuclein and polyunsaturated fatty acids promote clathrin-mediated endocytosis and synaptic vesicle recycling
AU - Gedalya, Tziona Ben
AU - Loeb, Virginie
AU - Israeli, Eitan
AU - Altschuler, Yoram
AU - Selkoe, Dennis J.
AU - Sharon, Ronit
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
KW - Clathrin-mediated endocytosis
KW - Membrane fluidity
KW - Membrane trafficking
KW - Parkinson's disease
KW - Polyunsaturated fatty acids
KW - Synaptic vesicle recycling
KW - α-synuclein
UR - http://www.scopus.com/inward/record.url?scp=58549089901&partnerID=8YFLogxK
U2 - 10.1111/j.1600-0854.2008.00853.x
DO - 10.1111/j.1600-0854.2008.00853.x
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C2 - 18980610
AN - SCOPUS:58549089901
SN - 1398-9219
VL - 10
SP - 218
EP - 234
JO - Traffic
JF - Traffic
IS - 2
ER -