scholarly journals Prenatal overexpression of platelet‐derived growth factor receptor A results in central nervous system hypomyelination

2021 ◽  
Author(s):  
Herminio Joey Cardona ◽  
Agila Somasundaram ◽  
Donna M. Crabtree ◽  
Samantha L. Gadd ◽  
Oren J. Becher
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Growth Factor ◽  
Growth Factor Receptor ◽  
Platelet Derived Growth Factor

scholarly journals Loss of PRMT5 promotes PDGFRα degradation during oligodendrocyte differentiation and myelination

2018 ◽  
Author(s):  
Sara Calabretta ◽  
Gillian Vogel ◽  
Zhenbao Yu ◽  
Karine Choquet ◽  
Lama Darbelli ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Growth Factor ◽  
Cell Surface ◽  
Growth Factor Receptor ◽  
Arginine Methylation ◽  
Platelet Derived Growth Factor ◽  
Oligodendrocyte Differentiation ◽  
The Central Nervous System ◽  
Cns Myelination

SummaryPlatelet derived growth factor receptor α (PDGFRα) signaling is required for proliferation, commitment and maintenance of oligodendrocyte (OL) precursor cells (OPCs). PDGFRα signaling promotes OPC homeostasis and its attenuation signals OPC differentiation and maturation triggering the onset of myelination of the central nervous system (CNS). The initial steps of how PDGFRα signaling is attenuated are still poorly understood. Herein we show that decreased Protein Arginine MethylTransferase5 (PRMT5) expression, as occurs during OPC differentiation, is involved in the down-regulation of PDGFRα by modulating its cell surface bioavailability leading to its degradation in a Cbldependent manner. Mechanistically, loss of arginine methylation at R554 of the PDGFRα intracellular domain reveals a masked Cbl binding site at Y555. Physiologically, depletion of PRMT5 in OPCs results in severe CNS myelination defects. We propose that decreased PRMT5 activity initiates PDGFRα degradation to promote OL differentiation. More broadly, inhibition of PRMT5 may be used therapeutically to manipulate PDGFRα bioavailability.

A role for platelet-derived growth factor in normal gliogenesis in the central nervous system

Cell ◽  
1988 ◽  
Vol 53 (2) ◽  
pp. 309-319 ◽  
Author(s):  
William D. Richardson ◽  
Nigel Pringle ◽  
Michael J. Mosley ◽  
Bengt Westermark ◽  
Monique Dubois-Dalcg
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Growth Factor ◽  
Platelet Derived Growth Factor ◽  
The Central Nervous System
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