Selective Autophagy in the CNS

Identification: Yamamoto, Ai


Description

Selective Autophagy in the CNS
 
Ai Yamamoto
Columbia University, New York, New York, USA
 
Disrupting the ability to degrade cargoes selectively by macroautophagy (MA) has been implicated to be at the heart of a wide array of neurodevelopmental and neurological diseases. Nevertheless little is understood about the basal role of selective MA in the healthy brain. Understanding how this pathway impacts the different cells of the central nervous system (CNS) will not only help us gain insight into pathological processes, but due to the fundamental importance of MA in all cell types, it will help us gain insight into the mystery shrouding many of these cells. One example of a mysterious cell type in the CNS is highly specialized cells known as oligodenodrocytes (OLs). OLs extend numerous processes with which they form myelin sheaths around most axons in the CNS, which permit the rapid and reliable conduction of neuronal action potentials.  Contrary to the static nature previously ascribed to OLs, we find that selective MA in OLs is essential for these cells to continuously remodel pre-existing myelin sheaths. Interestingly, MA is dispensable during development, but instead leads to an age-dependent increase in myelin thickness, abnormal myelin structures and premature death, suggesting that unlike during the formation of the OLs, selective MA is essential once the cell becomes highly compartmentalized. We find that in a selective manner, proteins associated with myelin are packaged into the autophagosome, and through the formation of the amphisome, leads to myelin turnover. Thus by determining the importance of selective MA in OLs, we find that OLs are dynamic cells that can modulate myelin thickness, thereby leading to implications for how activity-dependent myelination may play a far more active role modulating neuronal circuitry.
 
 
 

Credits

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