Identification of two distinct synucleins from human brain

Abstract

AbstTPCtTwo abundant proteins of 140 and 134 amino acids were puritied and sequenced from human brain. They were identfied through their reactivity on immunoblots with a partially characterised monoclonal antibody that recognises tau protein in a phosphorylation-dependent manner. The 140 amino acid protein is identical with the precursor of the non-M component of Alxheimer's disease amyloid which in turn is highly homologous to synuclein from Torpedo electroplaques and rat brain. The 134 amino acid protein is the human homologue of bovine phosphoneuroprotein 14, it is 61% identical in sequence to the 140 amino acid protein, The previously unrecognised homology between these two proteins defines a family of human brain synucleins. We refer to the 140 and 134 amino acid proteins as a-synuclein and /I-synuclein, respectively. Both synucleins are expressed predominantly in brain, where they are concentrated in presynaptic nerve terminals.

Alpha synuclein is present in Lewy bodies in sporadic Parkinson's disease

“…This protein and its homologues have been isolated from fish, rats, birds and humans. 4,5 It appears to reside in nerve terminals and the only function known to date is an involvement in the song learning process in the zebra finch. 6 The human protein was initially identified because a peptide fragment of alpha synuclein was found in plaques of patients with Alzheimer's disease, suggesting that mutations in this gene might be responsible for some cases of Alzheimer's disease.…”

α-Synuclein interacts with the switch region of Rab8a in a Ser129 phosphorylation-dependent manner

“…bound Rab8a in our in vitro measurements, which employed soluble Rab8a and αS. In addition, it is important to keep in mind that αS is highly abundant in neuronal systems (Jakes et al, 1994;Iwai et al, 1995) and a large excess of αS could favor binding to Rab8a. Indeed, triplication of the αS locus was shown to cause PD and αS progressively accumulates in cytosolic vesicles and the ER during disease (Cooper et al, 2006;Colla et al, 2012).…”

“…Introduction α-Synuclein (αS) is a widely abundant protein in the central nervous system (Jakes et al, 1994;Iwai et al, 1995). Multiplications of the SNCA gene, which encodes αS (Chartier-Harlin et al, 2004), as well as point mutations in αS cause autosomal dominant forms of Parkinson's disease (PD) (Hardy et al, 2009), a disease that affects several brain areas during its progression (Braak et al, 2003).…”

Molecular mechanisms for aberrant expression of the human breast cancer specific gene 1 in breast cancer cells: control of transcription by DNA methylation and intronic sequences

“…The BCSG1 gene is transcribed into a 1 kb mRNA, and encodes a 127-amino acid polypeptide. Comparison of the predicted amino acid sequence with genetic databases reveals that BCSG1 is highly homologous to a family of neuronal cytosolic proteins, namely synucleins that are mainly expressed in brain and are localized to presynaptic terminals (Ueda et al, 1993;Jakes et al, 1994;Xia et al, 1996). BCSG1 shares 54 and 56% amino acid sequence identity with synuclein a and synuclein b respectively.…”