|
KMID : 0578320220450080537
|
|
Molecules and Cells
2022 Volume.45 No. 8 p.537 ~ p.549
|
|
|
Transcriptional Regulatory Role of NELL2 in Preproenkephalin Gene Expression
|
|
Ha Chang-Man
Kim Dong-Hee
Lee Tae-Hwan
Kim Han-Rae
Choi Jung-Il
Kim Yoon-Ju
Kang Da-Sol
Park Jeong-Woo
Ojeda Sergio R.
Jeong Jin-Kwon
Lee Byung-Ju
|
|
|
Abstract
|
|
|
|
Preproenkephalin (PPE) is a precursor molecule for multiple endogenous opioid peptides Leu-enkephalin (ENK) and Met-ENK, which are involved in a wide variety of modulatory functions in the nervous system. Despite the functional importance of ENK in the brain, the effect of brain-derived factor(s) on PPE expression is unknown. We report the dual effect of neural epidermal growth factor (EGF)-likelike 2 (NELL2) on PPE gene expression. In cultured NIH3T3 cells, transfection of NELL2 expression vectors induced an inhibition of PPE transcription intracellularly, in parallel with downregulation of protein kinase C signaling pathways and extracellular signal-regulated kinase. Interestingly, these phenomena were reversed when synthetic NELL2 was administered extracellularly. The in vivo disruption of NELL2 synthesis resulted in an increase in PPE mRNA level in the rat brain, suggesting that the inhibitory action of intracellular NELL2 predominates the activation effect of extracellular NELL2 on PPE gene expression in the brain. Biochemical and molecular studies with mutant NELL2 structures further demonstrated the critical role of EGF-like repeat domains in NELL2 for regulation of PPE transcription. These are the first results to reveal the spatio-specific role of NELL2 in the homeostatic regulation of PPE gene expression.
|
|
|
KEYWORD
|
|
|
calcium ion, endoplasmic reticulum, extracellular signal-regulated kinase, NELL2, preproenkephalin, protein kinase C
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
  
|