Dual regulation of mast cell degranulation through IgE receptor-mediated modulation of $M_2$-type pyruvate kinase

Zheng, Mei,Cho, Dong-Im,Le, Hang Thi,Cheon, Seung Hoon,Kim, Kyeong-Man 대한약학회 2014 Archives of Pharmacal Research Vol.37 No.9

It was reported that mast cell degranulation is inversely related to the enzymatic activity of $M_2$-type pyruvate kinase ($M_2PK$). This study shows that activation of high-affinity IgE receptor ($Fc{\varepsilon}RI$) evokes a sequential dual regulation of $M_2PK$, i.e., an immediate decrement followed by slow phase increment of enzymatic activities. Changes in the activities of $M_2PK$ and mast cell degranulation showed similar time course after antigenic stimulation of $Fc{\varepsilon}RI$. The immediate inhibition of $M_2PK$ involved tyrosine phosphorylation, and subsequently led to a cellular accumulation of glycolytic intermediates, including fructose 1,6-biphosphate (FBP), a feedforward activator of $M_2PK$. As the cellular levels of FBP were increased, both the enzymatic acitivity of $M_2PK$ and mast cell degranulation slowly returned to near basal levels. A-Raf, when exogenously introduced into RBL-2H3 cells, phosphorylated $M_2PK$ on the serine residues, elevated enzyme activities of $M_2PK$, and resulted in the inhibition of degranulation. These results suggest that dual regulation of $M_2PK$ which involves the phosphorylation of $M_2PK$ and accumulation of a feedforward activator of $M_2PK$ plays important roles in the control of mast cell degranulation.

Functional Regulation of Dopamine D₃ Receptor through Interaction with PICK1

Zheng, Mei,Zhang, Xiaohan,Min, Chengchun,Choi, Bo-Gil,Oh, In-Joon,Kim, Kyeong-Man The Korean Society of Applied Pharmacology 2016 Biomolecules & Therapeutics(구 응용약물학회지) Vol.24 No.5

PICK1, a PDZ domain-containing protein, is known to increase the reuptake activities of dopamine transporters by increasing their expressions on the cell surface. Here, we report a direct and functional interaction between PICK1 and dopamine $D_3$ receptors ($D_3R$), which act as autoreceptors to negatively regulate dopaminergic neurons. PICK1 colocalized with both dopamine $D_2$ receptor ($D_2R$) and $D_3R$ in clusters but exerted different functional influences on them. The cell surface expression, agonist affinity, endocytosis, and signaling of $D_2R$ were unaffected by the coexpression of PICK1. On the other hand, the surface expression and tolerance of $D_3R$ were inhibited by the coexpression of PICK1. These findings show that PICK1 exerts multiple effects on $D_3R$ functions.

ALKBH8B, a Putative RNA Demethylase, Plays a Role in the Response of Arabidopsis to Salt Stress and Abscisic Acid

Huong Trinh Thi,Yang Zhengmei,Ngoc Le Nguyen Tieu,강훈승 한국식물학회 2022 Journal of Plant Biology Vol.65 No.4

RNA methylation and demethylation, which are mediated by RNA methyltransferases (referred to as “writers”) and demethylases (referred to as “erasers”), respectively, have increasingly been demonstrated to play crucial roles in stress responses as well as in plant development. The Arabidopsis thaliana genome encodes thirteen AlkB homolog (ALKBH) proteins that are potential RNA demethylases; however, the functions of most ALKBHs are yet to be determined. In this study, we characterized the function of a potential eraser protein ALKBH8B (At4g02485) during seed germination and seedling growth of Arabidopsis under abiotic stresses. Confocal analysis of the ALKBH8B-GFP expression confirmed that ALKBH8B is localized in the nucleus. The loss-of-function alkbh8b mutant exhibited no apparent phenotypes compared with the wild type under normal and abiotic stress conditions. In contrast, the ALKBH8B-overexpressing transgenic Arabidopsis plants displayed salt-tolerant phenotypes exhibiting better seedling growth and survival rate than wild-type under salt stress. Notably, salt tolerance of the transgenic plants was associated with up- and down-regulation of the expression of several m6A-modified salt stress positive and negative regulators, respectively. Moreover, cotyledon greening and seedling growth of the ALKBH8B-overexpressing transgenic plants were much higher than those of wild type upon abscisic acid (ABA) application, and the transcript levels of ABA signaling-related genes, such as ABI3 and ABI4 were markedly decreased in the transgenic plants. Importantly, global m6A levels decreased in the ALKBH8B-overexpressing transgenic plants as compared with the wild type. Collectively, these results indicate that ALKBH8B plays a role in the response of Arabidopsis to salt stress and ABA via modulating the expression of salt stress- or ABA signaling-related genes.

Genome-wide identification, characterisation and expression profile analysis of DEAD-box family genes in sweet potato wild ancestor Ipomoea trifida under abiotic stresses

Rong Wan,Jingran Liu,Zhengmei Yang,Panpan Zhu,Qinghe Cao,Tao Xu 한국유전학회 2020 Genes & Genomics Vol.42 No.3

Background DEAD-box protein family is the largest subfamily of RNA helicases and plays an important role in RNA metabolism and plant growth, development, and stress responses. Although DEAD-box genes have been characterized in various major crop plants, their identification and characterization in Convolvulaceae is still in infancy. Sweet potato (Ipomoea batatas, in Convolvulaceae) is the seventh most important crop in the world. Ipomoea trifida is one of the ancestors of sweet potato and is an effective resource for sweet potato cross-breeding. Objective Identification and characterisation of DEAD-box transcription factors in sweet potato wild ancestor I. trifida genome. Method A systematic genome-wide analysis was conducted to identify the DEAD-box transcription factors in the I. trifida genome. Results We identified 17 ItfDEAD-box genes which distributed unevenly on the nine chromosomes of I. trifida and encoded 29 DEAD transcripts. The phylogenetic analysis classified the DEAD-box proteins into nine groups named I–IX. Homology model prediction of ItfDEAD-box proteins obtained 14 models which lay a preliminary foundation for the further functional exploration of the ItfDEAD-box proteins. The tissue-specific and abiotic stress-responsive expression profiles of ItfDEAD-box genes were analyzed in different tissues and under abiotic stress responses by RNA-seq data and confirmed by quantitative PCR analysis. Some genes were significantly up- or down-regulated by different abiotic stress, suggesting that ItfDEAD-box plays a crucial role in stress responses in I. trifida. Conclusion The identification and gene expression of the ItfDEAD-box gene family might shed light on the function exploration of DEAD-box gene in I. trifida and promote the molecular breeding of sweet potato.

The Role of Bone Marrow Stromal Cell Antigen 2 (BST2) in the Development of Collagen-induced Arthritis (CIA)

Jae-Myeong JEON,Jin-Soo OH,Se-Hoon PARK,ZHENGMEI XU,Se-Ho PARK 한국생물공학회 2021 한국생물공학회 학술대회 Vol.2021 No.10

Bone marrow stromal antigen 2 (BST2) is an innate immune molecule involved in anti-viral immune responses and is highly expressed on the plasmacytoid dendritic cells (pDCs), a major cell type producing type І IFNs, BST2 also involved in the regulation of CCR7 and LFA-1 expression on the conventional dendritic cells (cDCs), well known professional antigen presenting cells. Because type І IFNs and self-antigen presentation by cDCs are important regulating factors in the initiation and progression of autoimmune diseases, we investigated the roles of BST2 in the development of autoimmune diseases using collagen-induced arthritis (CIA) model. Compared to BST2-hetero (BST2<SUP>+/-</SUP>) mice, BST2 deficient (BST2<SUP>-/-</SUP>) mice showed significantly lower disease scores and lower serum level of collagen-specific immunoglobulins. H&E staining also showed reduce infiltration of inflammatory cells in the joints of BST2<SUP>-/-</SUP> mice compared to those of BST2-hetero (BST2<SUP>+/-</SUP>) mice. Our results suggest that BST2 can be a potential therapeutic target for the treatment of autoimmune diseases especially rheumatoid arthritis.