Session Information
Date: Wednesday, September 25, 2019
Session Title: Physiology and Pathophysiology
Session Time: 1:15pm-2:45pm
Location: Les Muses, Level 3
Objective: This study aims to uncover the prospective partner of αS in nucleus.
Background: In neuronal cells, large part of alpha-synuclein (αS) localize at presynaptic terminal, while it is also be evident that αS reside in nucleus. Our concern is how αS behave in that field. In recent study, we found some important neuronal genes bonded by tight cores of methylated histone H3 in the presence of αS. Shaping those forms, epigenetic effectors coacting with αS should be existed. To release the tangled chains affecting degenerative process of synucleinopathy, it would be unavoidable step to unveil the partner engaged with αS.
Method: Fine nuclear lysates were extracted from 293 cells stably expressing HA-tagged αS using modified standard method. To avoid non-specific binding of nucleic acids to the sepharose beads, RNAse, DNAse, and Benzonaze were supplemented with the buffers. 800 ug of nuclear lysates were incubated with anti-HA antibody-conjugated-beads overnight. After intensive washes, HA-αS interacting proteins were competitively collected by HA peptides. Digested samples were thoroughly analyzed by nanoLC-MS/MS. Protein, which had at least 5 spectral counts (SpC) in the HA-αS sample, which was not detected in the parental 293 sample, and which was detected with a 4-fold or more increase based on dividing SpC values, were given as meaningful binding.
Results: Based on the criteria described above, 216 nuclear proteins were qualified. Functionally, several of them were member of BAF (BRG1-Associated Factor) complex by which some of the components are replaced to another during neuronal differentiation. In mature neuronal cells as well as 293 cells, αS was interacted with SMARCC1 and SMARCC2, key players of that complex. Furthermore, switching of developmental components was robustly disturbed in the presence of αS.
Conclusion: We found putative αS-interacting proteins belong to BAF complex. αS may alter the physiological function of that complex.
References: 1. Sugeno N, Jackel S, Voigt A, et al. (2016) alpha-Synuclein enhances histone H3 lysine-9 dimethylation and H3K9me2-dependent transcriptional responses. Scientific reports 6: 36328
To cite this abstract in AMA style:
N. Sugeno, T. Hasegawa, J. Kobayashi, S. Yoshida, M. Ezura, A. Kikuchi, A. Takeda, M. Aoki. Alpha-synuclein interacts with BAF complex in nucleus [abstract]. Mov Disord. 2019; 34 (suppl 2). https://www.mdsabstracts.org/abstract/alpha-synuclein-interacts-with-baf-complex-in-nucleus/. Accessed June 14, 2025.« Back to 2019 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/alpha-synuclein-interacts-with-baf-complex-in-nucleus/