Semi-quantitative analysis of α-synuclein in subcellular pools of rat brain neurons: An immunogold electron microscopic study using a C-terminal specific monoclonal antibody

Domain a’ of protein disulfide isomerase plays key role in inhibiting α-synuclein fibril formation

“…c ITC data of binding of the PDI proteins to αSyn at 25°C: squares represent the integrated binding isotherm at each injection after dilution heat effect correction and molar concentration based normalization, solid lines represent the non-linear least squares fit to a three sequential binding sites model, and the best fit parameters of dissociation constant K d for the first binding event are indicated therein αSyn has recently been shown to be implicated in ER impairment and ER stress (Wang and Takahashi 2007), however, the mechanism remains unknown. It was found that αSyn is more concentrated in ER than in cytoplasmic region (Zhang et al 2008). Our data provide direct evidence for the interactions between αSyn and PDI, and suggest that PDI, a key component of the protein quality control system in the ER, may counteract the toxicity of αSyn in the ER by binding oligomeric αSyn formed in the early stage and finally inhibiting fibril formation.…”

“…In immunogold electron microscopy examination of rat brain neurons, the αSyn concentration was found to be higher in endoplasmic reticulum (ER) than in cytoplasmic region (Zhang et al 2008). Synthesized αSyn in yeast was found to be translocated from the ER to the Golgi and further to the plasma membrane through a classical secretion pathway (Dixon et al 2005).…”

Familial Parkinson Disease-associated Mutations Alter the Site-specific Microenvironment and Dynamics of α-Synuclein

“…Analysis of Fluorescence Anisotropy Decay Kinetics-The time-resolved anisotropy decay curves were derived using Equation 3.…”

“…The substituted Trp residues are shown in blue, and the rectangular boxes indicate the mutation site in the sequences. To delineate the site-specific structural dynamics of ␣-Syn, freshly prepared low molecular weight solutions of Trp 3 (Fig. 1, C and D).…”

“…nucleus and presynaptic terminals of neurons with some fractions existing in association with the synaptic vesicles (2)(3)(4). Although the physiological function of ␣-Syn has not been fully determined, it has been suggested to play a role in neurotransmitter (dopamine) release and regulation of the reserve pool of synaptic vesicles at nerve terminals (5,6).…”