Abstract
ABSTRACTAfter axonal injury, chromatolysis (fragmentation of Nissl substance) can occur in the soma. Electron microscopy shows that chromatolysis involves fission of the rough endoplasmic reticulum. In CNS neurons (which do not regenerate axons back to their original targets) or in motor neurons or dorsal root ganglion neurons denied axon regeneration (e.g., by transection and ligation), chromatolysis is often accompanied by degranulation (loss of ribosomes from rough endoplasmic reticulum), disaggregation of polyribosomes and degradation of monoribosomes into dust‐like particles. Ribosomes and rough endoplasmic reticulum may also be degraded in autophagic vacuoles by ribophagy and reticulophagy, respectively. In other words, chromatolysis is disruption of parts of the protein synthesis infrastructure. Whereas some neurons may show transient or no chromatolysis, severely injured neurons can remain chromatolytic and never again synthesize normal levels of protein; some may atrophy or die. Ribonuclease(s) might cause the following features of chromatolysis: fragmentation and degranulation of rough endoplasmic reticulum, disaggregation of polyribosomes and degradation of monoribosomes. For example, ribonucleases in the EndoU/PP11 family can modify rough endoplasmic reticulum; many ribonucleases can degrade mRNA causing polyribosomes to unchain and disperse, and they can disassemble monoribosomes; Ribonuclease 5 can control rRNA synthesis and degrade tRNA; Ribonuclease T2 can degrade ribosomes, endoplasmic reticulum and RNA within autophagic vacuoles; and Ribonuclease IRE1α acts as a stress sensor within the endoplasmic reticulum. Regeneration might be improved after axonal injury by protecting the protein synthesis machinery from catabolism; targeting ribonucleases using inhibitors can enhance neurite outgrowth and could be a profitable strategy in vivo. © 2018 Wiley Periodicals, Inc. Develop Neurobiol, 2018
Highlights
(fragmentation of Nissl substance) can occur in the soma
Electron microscopy reveals that Nissl bodies are parallel arrays of cisterns of rough endoplasmic reticulum studded with ribosomes; rosettes of free
Each ribosome is a complex of ribosomal RNAs and proteins that use transfer RNAs and amino acids to synthesize proteins from mRNAs
Summary
RNase 1 (Saxena et al, 1992) RNase 2 (Saxena et al, 1992) Polysome-Bound Endonuclease (PMR1) (Schoenberg and Maquat, 2012) GTPase-activating protein binding protein (G3BP-1) (Schoenberg and Maquat, 2012) IRE1a (Li et al, 2013) Ribonuclease T2 (Haud et al, 2011) RNase 5 (Saxena et al, 1992; Pizzo et al, 2013) RNase 1 can cause dose-dependent changes in endoplasmic reticulum whilst EndoU/PP11 ribonucleases can dynamically regulate smooth and rough endoplasmic reticulum (Schwarz and Blower, 2014) Not known RNase T2 (Haud et al, 2011) Ribonuclease 1 (Gerashchenko and Gladyshev, 2017) RNase T2 (Haud et al, 2011) and Ribonuclease 1 (Gerashchenko and Gladyshev, 2017) RNase 5 IRE1a (Li et al, 2013). It is possible that chromatolysis may be due to uptake of a ribonuclease from the extracellular environment after injury; this would need to be reconciled with the fact that chromatolysis tends to start centrally, sometimes (but not always) with sparing of peripheral rims of Nissl (Barron, 2004) It is not known what causes fragmentation or disarray of rough endoplasmic reticulum in chromatolytic neurons. Extensive and rapid fission of endoplasmic reticulum in CNS dendrites can be triggered by increases in intracellular calcium in vitro and in adult cortical neurons during global ischemia in vivo (Kucharz et al, 2009; Kucharz et al, 2011, 2013; Zhao and Blackstone, 2014) This process is reversible: fusion of fragments occurs if the fissile stimulus (e.g., K1) is washed out or if an NMDA receptor antagonist is applied (Kucharz et al, 2013). If ribonuclease activity remains increased persistently in CNS or PNS neurons, this could help explain atrophy and failure of long-distance axon regeneration after proximal CNS injury
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