mRNA Transport and Local Translation in Glia

Abstract

Though mRNA transport and local translation are extensively studied in neurons, emerging evidence supports that these cellular processes are also abundant in non-neuronal glial cells. Here, we explore mechanisms of mRNA transport and local translation in oligodendrocytes, astrocytes, microglia, radial glia, and their functions in development, structure, and intercellular interactions.

Figure 1 -. mRNA Transport and Local Translation in Glial Functions

A. In oligodendrocytes (pink), many mRNA cargos have now been demonstrated to be transported to myelin sheaths that surround neuronal axons (yellow). A canonical mRNA cargo is Mbp (myelin basic protein, inset), which is the most abundant mRNA in this cell type. Mbp mRNAs are transported along microtubules by the kinesin KIF1B and the dynein/dynactin motor complex to myelin sheaths. Multiple motifs (not pictured), such as “motif 2” and RTS (RNA transport signal), are important for Mbp mRNA localization. B. In astrocytes (blue), mRNAs are transported along processes and eventually arrive at either endfeet that contact blood vessels (red) or at terminals that contact the tripartite synapse (neuronal synapses picture in yellow). For example, the mRNA transcript Sparc is transported along microtubules in a complex that contains the RBP (RNA-binding protein) Quaking (QKI) (middle inset). At the endfeet (top inset), locally translated transcripts encode secreted proteins and plasma membrane proteins. At tripartite synapses (bottom inset), locally translated transcripts encode motor proteins, glutamate transporters, synapse regulators, and lipid processing proteins. C. In microglia (green), distal processes contain mRNAs that encode ribosomal proteins and that are involved in pathogen defense, motility, and phagocytosis (inset). D. Radial glia cells (orange), which are found in the cortex of the developing brain (left), rely on local translation in both apical and basal endfeet to define cell fates after asymmetric division. For example, at the basal endfeet (top inset), the transcripts Nestin, Arhgap11a, and Ccnd2 are locally translated. The RBP FMRP (fragile X mental retardation protein) participates in the transport of many mRNAs encoding cytoskeletal and motor proteins along the basal processes.