Origin of axonal proteins: Is the axon-schwann cell unit a functional syncytium?

Abstract

The structural homeostasis is challenging for neurons, whose axons extend up to meters in large animals, and the axoplasmic mass reaches over a thousand times that of the cell body. Thus, the protein demand may overcome the capacity of the cell body to supply the right protein species, to the right place, in the right time. In this context, a body of evidence indicates that glial cells support the axonal maintenance and regenerative responses by diverse mechanisms of intercellular communication. We showed recently that Schwann cells (SC) transfer ribosomes to axons and also enhance regeneration by means of extracellular vesicles known as exosomes that contain mRNAs, miRNAs and proteins. These findings strongly suggest that the nucleus of the SC supports the machinery for protein synthesis of the axon and participates in the specification of the phenotype of the underlying axon. That the genetic programs of many nuclei modulate the axoplasm on a local basis is akin to a syncytium but at variance with it, the nuclei belong to satellite cells. We propose that the SC-axon unit is a functional syncytium. This intercellular organization opens a novel understanding of the nervous system and a new avenue of research into its physiology and disorders.

The structural homeostasis is challenging for neurons, whose axons extend up to meters in large animals, and the axoplasmic mass reaches over a thousand times that of the cell body. Thus, the protein demand may overcome the capacity of the cell body to supply the right protein species, to the right place, in the right time. In this context, a body of evidence indicates that glial cells support the axonal maintenance and regenerative responses by diverse mechanisms of intercellular communication. We showed recently that Schwann cells (SC) transfer ribosomes to axons and also enhance regeneration by means of extracellular vesicles known as exosomes that contain mRNAs, miRNAs and proteins. These findings strongly suggest that the nucleus of the SC supports the machinery for protein synthesis of the axon and participates in the specification of the phenotype of the underlying axon. That the genetic programs of many nuclei modulate the axoplasm on a local basis is akin to a syncytium but at variance with it, the nuclei belong to satellite cells. We propose that the SC-axon unit is a functional syncytium. This intercellular organization opens a novel understanding of the nervous system and a new avenue of research into its physiology and disorders.