The local protein expression system in neurons

Gene expression, the process by which information from DNA is converted into mRNA and used in the synthesis of a functional gene product such as a protein, is the foundation of all life. Within neurons there is one essential aspect of the gene expression system that takes place in a decentralized manner. Neurons consist of the soma which contains a nucleus and the neurites that stretch out from it. In addition to the centralized gene expression system of the soma there also exists a decentralized gene expression system that provides local protein synthesis from mRNA in neurites at just the right time and place. It is believed that this system controls the location at which neuritis will connect to each other, thereby forming neural networks. Our laboratory is researching the types of mRNA and the mechanisms of this local protein synthesis in order to better understand its relation to the formation of neural networks, memory, learning, and behavior.

Neurons have two types of neurites, axon and dendrites. Axon terminals of a neuron are attached to dendrites of other neurons, forming connections known as synapses. Synapses are the place where neural activity is transmitted from the axon terminal (presynapses) to the dendrites (postsynapses). Some specific mRNAs are transported from the soma to dendrites by macromolecular complexes called "RNA granules", and translated locally at postsynapses when the transmission happens (Figure 1).

A model for local translation in neuronal dendrites Figure 1. A model for local translation in neuronal dendrites

Specific mRNAs are recruited into RNA granules and transported to dendrites. Translation of mRNAs is induced locally upon synaptic stimulation, which modifies local postsynapses to regulate synaptic connection and network formation.

The mRNAs in the RNA granule are translationally silent during the transport and at non-stimulated postsynapses, but their translation is activated at postsynapses that receive inputs from presynapses (Figure 1).We have identified RNA granule protein 105 (RNG105), an RNA-binding protein, as a component of RNA granules. Our research until now suggests that RNG105 is responsible for mRNA transport to dendrites, dendrite integrity, synapse formation in dendrites, and the formation of neuronal networks (Figure 2).

Phase contrast images of primary cultured neurons Figure 2. Phase contrast images of primary cultured neurons

Wild-type neurons formed well-developed neural networks (Left). RNG105 knockout neurons formed poor networks compared to wild type (Right). Scale bar, 100 µm.

Synaptic stimulation leads to Na+ and Ca2+ influx to dendrites and the elevation of reactive oxygen species, which involves the risk of neuronal cell death. The results of our study also suggest that RNG105-mediated mRNA transport and local translation play roles in the protection of neurons from such risks.

Now, we are researching protein factors and cargo mRNAs in RNG105-localizing RNA granules. We aim to find the molecular mechanism regulating mRNA transport and local translation in order to better understand its relation to the formation of synapses and neural networks, learning, memory, and behavior using mice as model animals. We are also interested in the link between defects in the formation and function of RNA granules and disorders including neurodegenerative disease.

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