Abstract
In the rat, the α-synuclein gene is alternatively spliced and exists in three forms, rat synuclein 1 (rSYN1), synuclein 2 (rSYN2) and synuclein 3. rSYN2 cDNA encodes a 149 amino acid protein that is homologous to rSYN1 and human α-synuclein for the first 100 amino acids, but is divergent for the 49 amino acid carboxy-terminal region. We demonstrate here that rSYN2 forms small aggregates throughout the cytoplasm when overexpressed in human H4 cells, whereas rSYN1 expression is diffuse. Inhibition of the proteasome promotes the formation of larger, cytoplasmic rSYN2 inclusions in transfected cells. Although a survey of the available databases suggests that there is no human splice form equivalent of rSYN2, thus arguing against a direct role in Lewy body formation and Parkinson's disease, these data nonetheless suggest that modifications of the carboxy-terminal region of α-synuclein predispose it to inclusion formation.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 219-223 |
| Number of pages | 5 |
| Journal | Neuroscience Letters |
| Volume | 323 |
| Issue number | 3 |
| DOIs | |
| State | Published - May 3 2002 |
| Externally published | Yes |
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Keywords
- Aggregation
- Carboxy-terminus
- Lewy body
- Parkinson's disease
- Proteasome
ASJC Scopus subject areas
- Neuroscience(all)
Cite this
An alternatively spliced form of rodent α-synuclein forms intracellular inclusions in vitro : Role of the carboxy-terminus in α-synuclein aggregation. / McLean, Pamela J; Hyman, Bradley T.
In: Neuroscience Letters, Vol. 323, No. 3, 03.05.2002, p. 219-223.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - An alternatively spliced form of rodent α-synuclein forms intracellular inclusions in vitro
T2 - Role of the carboxy-terminus in α-synuclein aggregation
AU - McLean, Pamela J
AU - Hyman, Bradley T.
PY - 2002/5/3
Y1 - 2002/5/3
N2 - In the rat, the α-synuclein gene is alternatively spliced and exists in three forms, rat synuclein 1 (rSYN1), synuclein 2 (rSYN2) and synuclein 3. rSYN2 cDNA encodes a 149 amino acid protein that is homologous to rSYN1 and human α-synuclein for the first 100 amino acids, but is divergent for the 49 amino acid carboxy-terminal region. We demonstrate here that rSYN2 forms small aggregates throughout the cytoplasm when overexpressed in human H4 cells, whereas rSYN1 expression is diffuse. Inhibition of the proteasome promotes the formation of larger, cytoplasmic rSYN2 inclusions in transfected cells. Although a survey of the available databases suggests that there is no human splice form equivalent of rSYN2, thus arguing against a direct role in Lewy body formation and Parkinson's disease, these data nonetheless suggest that modifications of the carboxy-terminal region of α-synuclein predispose it to inclusion formation.
AB - In the rat, the α-synuclein gene is alternatively spliced and exists in three forms, rat synuclein 1 (rSYN1), synuclein 2 (rSYN2) and synuclein 3. rSYN2 cDNA encodes a 149 amino acid protein that is homologous to rSYN1 and human α-synuclein for the first 100 amino acids, but is divergent for the 49 amino acid carboxy-terminal region. We demonstrate here that rSYN2 forms small aggregates throughout the cytoplasm when overexpressed in human H4 cells, whereas rSYN1 expression is diffuse. Inhibition of the proteasome promotes the formation of larger, cytoplasmic rSYN2 inclusions in transfected cells. Although a survey of the available databases suggests that there is no human splice form equivalent of rSYN2, thus arguing against a direct role in Lewy body formation and Parkinson's disease, these data nonetheless suggest that modifications of the carboxy-terminal region of α-synuclein predispose it to inclusion formation.
KW - Aggregation
KW - Carboxy-terminus
KW - Lewy body
KW - Parkinson's disease
KW - Proteasome
UR - http://www.scopus.com/inward/record.url?scp=0037012778&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037012778&partnerID=8YFLogxK
U2 - 10.1016/S0304-3940(02)00154-4
DO - 10.1016/S0304-3940(02)00154-4
M3 - Article
VL - 323
SP - 219
EP - 223
JO - Neuroscience Letters
JF - Neuroscience Letters
SN - 0304-3940
IS - 3
ER -