title: Axonal maintenance, glia, exosomes, and heat shock proteins.
abstract: Of all cellular specializations, the axon is especially distinctive because it is a narrow cylinder of specialized cytoplasm called axoplasm with a length that may be orders of magnitude greater than the diameter of the cell body from which it originates. Thus, the volume of axoplasm can be much greater than the cytoplasm in the cell body. This fact raises a logistical problem with regard to axonal maintenance. Many of the components of axoplasm, such as soluble proteins and cytoskeleton, are slowly transported, taking weeks to months to travel the length of axons longer than a few millimeters after being synthesized in the cell body. Furthermore, this slow rate of supply suggests that the axon itself might not have the capacity to respond fast enough to compensate for damage to transported macromolecules. Such damage is likely in view of the mechanical fragility of an axon, especially those innervating the limbs, as rapid limb motion with high impact, like running, subjects the axons in the limbs to considerable mechanical force. Some researchers have suggested that local, intra-axonal protein synthesis is the answer to this problem. However, the translational state of axonal RNAs remains controversial. We suggest that glial cells, which envelop all axons, whether myelinated or not, are the local sources of replacement and repair macromolecules for long axons. The plausibility of this hypothesis is reinforced by reviewing several decades of work on glia-axon macromolecular transfer, together with recent investigations of exosomes and other extracellular vesicles, as vehicles for the transmission of membrane and cytoplasmic components from one cell to another.
authors.affiliation: Department of Neurobiology and Anatomy, Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA; Marine Biological Laboratory, Marine Biological Laboratory, Woods Hole, MA, 02543, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Tytell
authors.affiliation: Department of Anatomy, Case Western Reserve University School of Medicine, Cleveland, OH, 44106, USA.
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: Lasek
authors.affiliation: Laboratory of Neurochemistry, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, 20892, USA; Marine Biological Laboratory, Marine Biological Laboratory, Woods Hole, MA, 02543, USA.
authors.forename: Harold
authors.initials: H
authors.lastname: Gainer
keywords: Axonal maintenance; HSP; axoplasm; exosomes; glia; heat shock proteins