Synucleins and Gene Expression: Ramblers in a Crowd or Cops Regulating Traffic?

Alexei A. Surguchev,Andrei Surguchov

doi:10.3389/fnmol.2017.00224

Alexei A. Surguchev, Andrei Surguchov

Open Access

https://doi.org/10.3389/fnmol.2017.00224

Copy DOI

Abstract

Synuclein family consists of three members, α, β, and γ-synuclein. Due to their involvement in human diseases, they have been thoroughly investigated for the last 30 years. Since the first synuclein identification and description, members of this family are found in all vertebrates. Sequencing of their genes indicates high evolutionary conservation suggesting important function(s) of these proteins. They are small naturally unfolded proteins prone to aggregate, easily change their conformation, and bind to the membranes. The genes for α, β, and γ-synuclein have different chromosomal localization and a well preserved general organization composed of five coding exons of similar size. Three genes encoding synucleins are present in the majority of vertebrates, however, a variable number of synuclein genes are described in fishes of different species. An important question concerns their normal function in cells and tissues. α-Synuclein is implicated in the regulation of synaptic activity through regulation of synaptic vesicle release, while the physiological functions of two other members of the family is understood less clearly. Here we discuss recent results describing their role in the regulation of gene expression.

Highlights

Since the discovery of the first synuclein by Maroteaux et al (1988), the members of the synuclein family attract growing attention primarily as proteins implicated in neurodegenerative (α-synuclein) and neoplastic (γ-synuclein) diseases
During the late 1990s the popular theory to explain mechanisms causing α-synuclein aggregation in cellular milieu was a concept of macromolecular crowding (Minton, 1993, 1998; Uversky et al, 2001)
The presence of synucleins in the nucleus and their binding to DNA provides a possibility that such interaction affects transcription regulation and may change neuronal function (Ma et al, 2014; Surguchov, 2014)

Summary

Introduction

Since the discovery of the first synuclein by Maroteaux et al (1988), the members of the synuclein family attract growing attention primarily as proteins implicated in neurodegenerative (α-synuclein) and neoplastic (γ-synuclein) diseases. The effect of elevated synucleins level on expression of specific genes was significant, the exact molecular mechanisms was often unknown. Α-synuclein altered expression of several families of genes including genes responsible for apoptosis, stress response, transcription regulation, and membrane proteins (Baptista et al, 2003).

Results

Conclusion