Synuclein-1 is selectively up-regulated in response to nerve growth factor treatment in PC12 cells.
Mutations in the alpha-synuclein gene have recently been identified in families with inherited Parkinson's disease and the protein product of this gene is a component of Lewy bodies, indicating that alpha-synuclein is involved in Parkinson's disease pathogenesis. A role for normal alpha-synuclein in synaptic function, apoptosis or plasticity responses has been suggested. We show here that in rat pheochromocytoma PC12 cells synuclein-1, the rat homolog of human alpha-synuclein, is highly and selectively up-regulated at the mRNA and protein levels after 7 days of nerve growth factor treatment. Synuclein-1 expression appears neither sufficient nor necessary for the neuritic sprouting that occurs within 1-2 days of nerve growth factor treatment. Rather, it likely represents a component of a late neuronal maturational response. Synuclein-1 redistributes diffusely within the cell soma and the neuritic processes in nerve growth factor-treated PC12 cells. Cultured neonatal rat sympathetic neurones express high levels of synuclein-1, with a diffuse intracellular distribution, similar to neuronal PC12 cells. These results suggest that levels of synuclein-1 may be regulated by neurotrophic factors in the nervous system and reinforce a role for alpha-synuclein in plasticity-maturational responses. In contrast, there is no correlation between synuclein expression and apoptotic death following trophic deprivation.
Stefanis
L
L
Department of Neurology, Columbia University, New York, USA. ls76@columbia.edu
Kholodilov
N
N
Rideout
H J
HJ
Burke
R E
RE
Greene
L A
LA
D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D008969:Molecular Sequence Data; D020932:Nerve Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D016501:Neurites / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016716:PC12 Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013564:Sympathetic Nervous System / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051843:Synucleins; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology*; D051844:alpha-Synuclein
D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C497606:Snca protein, rat; D051843:Synucleins; D051844:alpha-Synuclein; D020932:Nerve Growth Factor