NMDA receptor activation stimulates transcription-independent rapid wnt5a protein synthesis via the MAPK signaling pathway.
Wnt proteins are emerging key regulators of the plasticity and functions of adult brains. However, the mechanisms by which the expression of Wnt proteins is regulated in neurons are unclear. Using cortical primary cultures, we show here that activation of NMDA receptors (NMDARs) induces rapid Wnt5a protein synthesis and secretion. This NMDAR-regulated Wnt5a synthesis does not require transcription and is a result of activity-dependent translation. We also show that NMDAR-regulated Wnt5a translation depends on MAPK signaling but not mTOR signaling. Our findings suggest that the synaptic activity of CNS neurons activates NMDARs, which in turn stimulate translation from stored Wnt5a mRNA via the MAPK signaling pathway.
School of Pharmaceutical Sciences and Laboratory Animal Center of Sun Yat-Sen University, Guangzhen, P, R, China.
Yichen
Y
Li
Bei
B
Li
Xianzi
X
Wan
Wei
W
Zhang
Ling
L
Zhong
Shao-Jun
SJ
Tang
D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D020935:MAP Kinase Signaling System; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D014176:Protein Biosynthesis; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014158:Transcription, Genetic; D051153:Wnt Proteins / Q000096:biosynthesis*; D000071818:Wnt-5a Protein
D016194:Receptors, N-Methyl-D-Aspartate; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C438615:Wnt5a protein, mouse; D058570:TOR Serine-Threonine Kinases