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Mechanisms of slow axonal transport of α‐synuclein
Author(s) -
Roy Subhojit,
Winton Matthew J,
Black Mark M,
Trojanowski John Q,
Lee Virginia MY
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a28-d
Subject(s) - axoplasmic transport , alpha synuclein , neuroscience , synaptophysin , transport protein , axon , vesicular transport protein , biology , microbiology and biotechnology , chemistry , parkinson's disease , vesicle , biochemistry , pathology , medicine , disease , immunohistochemistry , membrane , immunology
Alpha‐synuclein inclusions are the neuropathologic hallmark of Parkinson's disease (PD). Alpha‐synuclein is synthesized in neuronal perikarya, transported into axons by slow axonal transport in a subgroup called slow component‐b (SCb), and subsequently enriches at presynapses. In PD, á‐synuclein accumulates in cell‐bodies and axons, indicating disruption of its axonal transport and/or presynaptic localization. Basic mechanisms of á‐synuclein transport in particular and SCb transport in general are unclear, as the transport has not been directly visualized. Using live‐cell imaging of fluorescent‐tagged human á‐synuclein, we have visualized its axonal transport and presynaptic localization in cultured hippocampal neurons from wild‐type and á‐synuclein −/− mice. We show that individual á‐synuclein particles are transported rapidly in axons but with pauses during transit resulting in a slow overall movement, unlike the fast transport protein synaptophysin, which moves much more frequently and persistently. By visualizing multiple SCb proteins simultaneously, we show that á‐synuclein is co‐transported with other SCb proteins, suggesting they move as protein complexes. Having clarified the underlying mechanisms of á‐synuclein transport in SCb, we have begun to explore the hypothesis that disease‐associated á‐synuclein mutants show defective transport/synaptic localization in neurons.