Protein phosphatase 2A facilitates axonogenesis by dephosphorylating CRMP2.
Protein phosphatase 2A (PP2A) is indispensable in development, and deficits of PP2A and deterioration of neuronal axons have been observed in several neurodegenerative disorders, but the direct link between PP2A and the neuronal axon development is still missing. Here, we show that PP2A is essential for axon development in transfected rat brain and the dissociated hippocampal neurons. Upregulation of PP2A catalytic subunit (PP2Ac) not only promotes formation and elongation of the functional axons but also rescues axon retardation induced by PP2A inhibition. PP2A can dephosphorylate collapsin response mediator protein-2 (CRMP2) that implements the axon polarization, whereas constitutive expression of phosphomimic-CRMP2 abrogates the effect of PP2A upregulation. We also demonstrate that PP2Ac is enriched in the distal axon of the hippocampal neurons. Our results reveal a mechanistic link between PP2A and axonogenesis/axonopathy, suggesting that upregulation of PP2A may be a promising therapeutic for some neurodegenerative disorders.
Zhu
Ling-Qiang
LQ
Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China.
Zheng
Hong-Yun
HY
Peng
Cai-Xia
CX
Liu
Dan
D
Li
Hong-Lian
HL
Wang
Qun
Q
Wang
Jian-Zhi
JZ
D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D001369:Axons / Q000201:enzymology* / Q000378:metabolism; D002478:Cells, Cultured; D018507:Gene Expression Regulation, Developmental; D006624:Hippocampus / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D016501:Neurites / Q000201:enzymology / Q000378:metabolism; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology*; D010766:Phosphorylation / Q000235:genetics; D054648:Protein Phosphatase 2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D034741:RNA, Small Interfering / Q000502:physiology; D051381:Rats
D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; C095114:collapsin response mediator protein-2; D054648:Protein Phosphatase 2