Identification and characterization of a new alpha-synuclein isoform and its role in Lewy body diseases.
Alternative splicing is an important mechanism to generate a large number of mRNAs, thus increasing proteome diversity and tissue specificity. Three transcript variants of alpha-synuclein, a neuronal protein mainly involved in synapses, have been described so far. Whereas alpha-synuclein 140 is the whole and main transcript, alpha-synuclein 112 and 126 are short proteins that result from in-frame deletions of exons 3 and 5, respectively. Because the aforesaid alpha-synuclein isoforms show differential expression changes in Lewy body diseases (LBDs), in the present work, we searched for a fourth alpha-synuclein isoform and studied its expression levels in LBD brains. By using isoform-specific primers, isoform co-amplification and direct sequencing, we identified alpha-synuclein 98, which lacks exons 3 and 5. mRNA expression analyses in non-neuronal tissue revealed that alpha-synuclein 98 is a brain-specific splice variant with varying expression levels in different areas of fetal and adult brain. Additionally, we studied alpha-synuclein 98 expression levels by real-time semi-quantitative RT-PCR in the frontal cortices of LBD patients and compared them with those of Alzheimer disease (AD) patients and control subjects. Overexpression of alpha-synuclein 98 in LBD and AD brains would indicate its specific involvement in the pathogenesis of these neurodegenerative disorders.
Beyer
Katrin
K
Department of Pathology, Hospital Universitari Germans Trias i Pujol, Autonomous University of Barcelona, Barcelona, Spain. katrinbeyer@hotmail.com
Domingo-Sábat
Montserrat
M
Lao
José I
JI
Carrato
Cristina
C
Ferrer
Isidro
I
Ariza
Aurelio
A
D000328:Adult; D017398:Alternative Splicing; D000544:Alzheimer Disease / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D001483:Base Sequence; D001921:Brain / Q000378:metabolism*; D016022:Case-Control Studies; D017931:DNA Primers / Q000235:genetics; D005091:Exons; D005333:Fetus / Q000378:metabolism; D005625:Frontal Lobe / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D020961:Lewy Body Disease / Q000209:etiology / Q000235:genetics* / Q000378:metabolism*; D008969:Molecular Sequence Data; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D051844:alpha-Synuclein / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*
D017931:DNA Primers; D020033:Protein Isoforms; D012333:RNA, Messenger; C497604:SNCA protein, human; D051844:alpha-Synuclein