miR-124 and miR-9 mediated downregulation of HDAC5 promotes neurite development through activating MEF2C-GPM6A pathway.
The class IIa histone deacetylases (HDACs) play important roles in the central nervous system during diverse biological processes such as synaptic plasticity, axon regeneration, cell apoptosis, and neural differentiation. Although it is known that HDAC5 regulates neuronal differentiation, neither the physiological function nor the regulation of HDAC5 in neuronal differentiation is clear. Here, we identify HDAC5 as an inhibitor of neurite elongation and show that HDAC5 is regulated by the brain enriched microRNA miR-124 and miR-9. We discover that HDAC5 inhibits neurite extension both in differentiated P19 cells and primary neurons. We also show that the neuronal membrane glycoprotein GPM6A (M6a) is a direct target gene of HDAC5 regulated transcriptional factor MEF2C. HDAC5 inhibits neurite elongation, acting at least partially via a MEF2C/M6a signaling pathway. We also confirmed the miR-124/miR-9 regulated HDAC5-MEF2C-M6a pathway regulates neurite development in primary neurons. Thus, HDAC5 emerges as a cellular conductor of MEF2C and M6a activity and is regulated by miR-124 and miR-9 to control neurite development.
Department of Neurobiology, Southern Medical University, Guangzhou, Guangdong Province, China.
Xi
http://orcid.org/0000-0001-9929-7630
X
Gu
Department of Neurobiology, Southern Medical University, Guangzhou, Guangdong Province, China.
Congcong
C
Fu
Meizhou People's Hospital, Meizhou Hospital Affiliated to Sun Yat-sen University, Meizhou, China.
Lifang
L
Lin
Department of Neurobiology, Southern Medical University, Guangzhou, Guangdong Province, China.
Shuhu
S
Liu
Department of Neurobiology, Southern Medical University, Guangzhou, Guangdong Province, China.
Xiaohong
X
Su
Department of Neurobiology, Southern Medical University, Guangzhou, Guangdong Province, China.
Aili
A
Li
Department of Neurobiology, Southern Medical University, Guangzhou, Guangdong Province, China.
Qiaoqi
Q
Wu
Department of Cell Biology, Southern Medical University, Guangzhou, Guangdong Province, China.
Chunhong
C
Jia
Department of Neurobiology, Southern Medical University, Guangzhou, Guangdong Province, China.
Peidong
P
Zhang
Department of Neurobiology, Southern Medical University, Guangzhou, Guangdong Province, China.
Lu
L
Chen
School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong Province, China.
Xinhong
X
Zhu
Department of Neurobiology, Southern Medical University, Guangzhou, Guangdong Province, China.
Xuemin
X
Wang
D000818:Animals; D015536:Down-Regulation; D053595:Embryonic Stem Cells / Q000187:drug effects / Q000201:enzymology*; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D005865:Gestational Age; D057809:HEK293 Cells; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D064326:MEF2 Transcription Factors / Q000235:genetics / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D058953:Neural Stem Cells / Q000187:drug effects / Q000201:enzymology*; D016501:Neurites / Q000187:drug effects / Q000201:enzymology*; D055495:Neurogenesis / Q000187:drug effects; D015398:Signal Transduction; D014162:Transfection
C083480:Gpm6a protein, mouse; D056572:Histone Deacetylase Inhibitors; D064326:MEF2 Transcription Factors; C551804:MIRN9 microRNA, mouse; C578041:Mef2c protein, mouse; D008562:Membrane Glycoproteins; D035683:MicroRNAs; C540079:Mirn124 microRNA, mouse; D009419:Nerve Tissue Proteins; C498618:Hdac5 protein, mouse; D006655:Histone Deacetylases
GPM6A; HDAC5; miR-124; miR-9; neurite development