PLCβ1 by-passes early growth response-1 to induce the differentiation of neuronal cells

被引:5
作者
Gonzalez-Burguera, Imanol [1 ,2 ]
Lin, Guanyu [3 ]
de Jesus, Maider Lopez [2 ,4 ]
Saumell-Esnaola, Miquel [2 ,4 ]
Barrondo, Sergio [2 ,4 ,5 ]
del Cano, Gontzal Garcia [1 ,2 ]
Salles, Joan [2 ,4 ,5 ]
Scarlata, Suzanne [3 ]
机构
[1] Univ Basque Country UPV EHU, Fac Pharm, Dept Neurosci, Vitoria 01006, Spain
[2] Bioaraba Neurofarmacol Celular & Mol, Vitoria 01006, Spain
[3] Worcester Polytech Inst, Dept Chem & Biochem, Worcester, MA 01609 USA
[4] Univ Basque Country UPV EHU, Fac Pharm, Dept Pharmacol, Vitoria 01006, Spain
[5] Ctr Invest Biomed Red Salud Mental CIBERSAM, Madrid 28029, Spain
关键词
PHOSPHOLIPASE-C-BETA; RETINOIC ACID; SUBCELLULAR-LOCALIZATION; BINDING-PROTEIN; NTERA-2; CELLS; TRANSPLANTATION; ASSOCIATION; C-BETA-1; THERAPY; STROKE;
D O I
10.1038/s41420-024-02009-z
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The G alpha q/phospholipase C-beta (PLC beta) signaling system mediates calcium responses to a variety of hormones and neurotransmitters. Recent studies suggest that PLC beta 1 expression plays a role in the differentiation of two types of cultured neuronal cells (PC12 and SK-N-SH) through a mechanism independent of G alpha q. Here, we show that, similar to that observed in PC12 and SK-N-SH cells, PLC beta 1 expression increases when human NT2 cells are induced to differentiate either through cytosine-beta-D-arabinofuranoside or retinoic acid. Preventing this increase, abolishes differentiation, and down-regulating PLC beta 1 in rat primary astrocytes causes cells to adapt an undifferentiated morphology. Surprisingly, transfecting PLC beta 1 into undifferentiated PC12 or NT2 cells induces differentiation without the need for differentiating agents. Studies to uncover the underlying mechanism focused on the transcription factor early growth response 1 (Egr-1) which mediates PLC beta 1 expression early in differentiation. Over-expressing PLC beta 1 in HEK293 cells enhances Egr-1 expression and induces morphological changes. We show that increased levels of cytosolic PLC beta 1 in undifferentiated PC12 cells disrupts the association between Egr-1 and its cytosolic binding partner (Tar RNA binding protein), promoting relocalization of Egr-1 to the nucleus, which promotes transcription of proteins needed for differentiation. These studies show a novel mechanism through which differentiation can be modulated.
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页数:11
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