Synuclein: a neuron-specific protein localized to the nucleus and presynaptic nerve terminal

Abstract

We used an antiserum against purified cholinergic synaptic vesicles from Torpedo and expression screening to isolate a cDNA clone encoding synuclein, a 143 amino acid neuron-specific protein. A cDNA clone was also isolated from a rat brain cDNA library that encodes a highly homologous 140 amino acid protein. The amino terminal 100 amino acids of both proteins are comprised of an 11 amino acid repeating unit that contains a conserved core of 6 residues. The synuclein gene is expressed only in nervous system tissue, not in electric organ, muscle, liver, spleen, heart, or kidney. In the electric organ synapse Torpedo synuclein-immunoreactive proteins are found in 3 major molecular-weight classes of 17.5, 18.5, and 20.0 kDa. In the neuronal cell soma the 17.5 kDa species is predominant and immunoreactivity is localized to a portion of the nuclear envelope.

Transcriptional dysregulation in a transgenic model of Parkinson disease

“…These data support the view that transcriptional dysregulation is an important consequence of α-syn overexpression and, therefore, may be critical to the pathogenesis of synucleinopathies. Alphasyn has been identified within cell nuclei and has been shown to associate with histones in vitro (Goers et al, 2003;Maroteaux et al, 1988). Studies by Kontopoulos et al (2006) have provided direct evidence that α-syn can inhibit histone acetylation in both mammalian cell culture models and transgenic Drosophila.…”

Alpha-synuclein deficiency and efferent nerve degeneration in the mouse cochlea: A possible cause of early-onset presbycusis

“…Four members of the synuclein family are known at present: ␣-synuclein, ␤-synuclein, ␥-synuclein, and synorectin (Maroteaux and Scheller, 1988;Surguchov et al, 1999). Alpha-synuclein has been identified as a component of the pathological inclusions of many neurodegenerative disorders, including Parkinson's disease, dementia with Lewy bodies, and multisystem atrophy (Tofaris, 2007).…”

19F NMR studies of α‐synuclein‐membrane interactions

“…1) is a 140 amino-acid, intrinsically-disordered protein associated with Parkinson's disease and other neurodegenerative disorders [1][2][3][4][5][6][7][8] whose function is hypothesized to involve its interaction with membranes. [8][9][10][11][12] The protein binds lipids and anionic detergents through the seven imperfect, cationic, 11-amino acid repeats located in its N-terminal and hydrophobic regions.…”