Altered Translational Control of Fragile X Mental Retardation Protein on Myelin Proteins in Neuropsychiatric Disorders

Abstract

Myelin is a specialized structure of the nervous system that both enhances electrical conductance and insulates neurons from external risk factors. In the central nervous system, polarized oligodendrocytes form myelin by wrapping processes in a spiral pattern around neuronal axons through myelin-related gene regulation. Since these events occur at a distance from the cell body, post-transcriptional control of gene expression has strategic advantage to fine-tune the overall regulation of protein contents in situ. Therefore, many research interests have been focused to identify RNA binding proteins and their regulatory mechanism in myelinating compartments. Fragile X mental retardation protein (FMRP) is one such RNA binding protein, regulating its target expression by translational control. Although the majority of works on FMRP have been performed in neurons, it is also found in the developing or mature glial cells including oligodendrocytes, where its function is not well understood. Here, we will review evidences suggesting abnormal translational regulation of myelin proteins with accompanying white matter problem and neurological deficits in fragile X syndrome, which can have wider mechanistic and pathological implication in many other neurological and psychiatric disorders.

Keywords: Fragile X mental retardation protein; Myelin; Oligodendrocyte; Translational control.

Fig. 1.

Schematic representation of local mRNA transport and translation in oligodendrocyte processes. Under physiological condition, FMRP (violet) and target mRNA (circles) mRNP components moves into distal process in association with motor proteins such as kinesin (blue circle), which usually kept relatively dormant until the activation. When exposed to an appropriate signal, the mRNP complex dissociates RBP such as FMRP, which initiates translation of mRNA locally, resulting in the increased protein synthesis specifically in places of activation.