Exosomes: mediators of communication in eukaryotes

In addition to the established mechanisms of intercellular signaling, a new way of communication has gained much attention in the last decade: communication mediated by exosomes. Exosomes are nanovesicles (with a diameter of 40-120 nm) secreted into the extracellular space by the multivesicular endosome after its outer membrane fuses with the plasma membrane. Once released, exosomes modulate the response of the recipient cells that recognize them. This indicates that exosomes operate in a specific manner and participate in the regulation of the target cell. Remarkably, exosomes occur from unicellular organisms to mammals, suggesting an evolutionarily conserved mechanism of communication. In this review we describe the cascade of exosome formation, intracellular traffic, secretion, and internalization by recipient cells, and review their most relevant effects. We also highlight important steps that are still poorly understood.

Slow axoplasmic transport under scrutiny

The origin of axoplasmic proteins is central for the biology of axons. For over fifty years axons have been considered unable to synthesize proteins and that cell bodies supply them with proteins by a slow transport mechanism. To allow for prolonged transport times, proteins were assumed to be stable, i.e., not degraded in axons. These are now textbook notions that configure the slow transport model (STM). The aim of this article is to cast doubts on the validity of STM, as a step toward gaining more understanding about the supply of axoplasmic proteins. First, the stability of axonal proteins claimed by STM has been disproved by experimental evidence. Moreover, the evidence for protein synthesis in axons indicates that the repertoire is extensive and the amount sizeable, which disproves the notion that axons are unable to synthesize proteins and that cell bodies supply most axonal proteins. In turn, axoplasmic protein synthesis gives rise to the metabolic model (MM). We point out a few inconsistencies in STM that MM redresses. Although both models address the supply of proteins to axons, so far they have had no crosstalk. Since proteins underlie every conceivable cellular function, it is necessary to re-evaluate in-depth the origin of axonal proteins. We hope this will shape a novel understanding of the biology of axons, with impact on development and maintenance of axons, nerve repair, axonopathies and plasticity, to mention a few fields.

Local regulation of the axonal phenotype, a case of merotrophism

In this essay, we show that several anatomical features of the axon, namely, microtubular content, caliber and extension of sprouts, correlate on a local basis with the particular condition of the glial cell, i.e., the anatomy of axons is dynamic, although it is seen usually in its `normal' state. The occurrence of ribosomes and messenger RNAs in the axon suggests that axoplasmic proteins are most likely synthesized locally, at variance with the accepted notion that they are supplied by the cell body. We propose that the supporting cell (oligodendrocyte or Schwann cell) regulates the axonal phenotype by fine-tuning the ongoing axonal protein synthesis.