Reduced neuritic outgrowth and cell adhesion in neuronal cells transfected with human alpha-synuclein.
Since recent reports have suggested that alpha-synuclein might play a role in neuronal plasticity, the main objective of this study was to determine the effects of alpha-synuclein on neuritic outgrowth. We stably transfected either human (h) alpha- or beta-synuclein cDNA in B103 rat neuronal cells. Expression of h(alpha)-synuclein resulted in reduced neurite extension and weak adhesion compared to vector-transfected and h(beta)-synuclein expressing cells. To investigate the potential pathways involved, we studied the effects of reagents known to modulate B103 proliferation and differentiation. Neither phorbol 12-myristate 13-acetate nor forskolin or antioxidants (catalase, superoxide dismutase, or vitamin E) were able to restore the reduced length of neurites in h(alpha)-synuclein-expressing cells. These results suggest that reduced neuritic activity in the h(alpha)-synuclein-expressing cells might be due, in part, to alterations in cell adhesion capacity. This might be attributed to alpha-synuclein affecting a signal transduction pathway distinct from protein kinase C and protein kinase A.
Takenouchi
T
T
Department of Neurosciences, University of California at San Diego, La Jolla, California, USA
Hashimoto
M
M
Hsu
L J
LJ
Mackowski
B
B
Rockenstein
E
E
Mallory
M
M
Masliah
E
E
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D051843:Synucleins; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection; D051844:alpha-Synuclein; D051846:beta-Synuclein
D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; C497607:SNCB protein, human; C497606:Snca protein, rat; C497609:Sncb protein, rat; D051843:Synucleins; D051844:alpha-Synuclein; D051846:beta-Synuclein; D005576:Colforsin; D013755:Tetradecanoylphorbol Acetate