TXNDC4
- Known as:
- TXNDC4
- Catalog number:
- Y213971
- Product Quantity:
- 200ul
- Category:
- -
- Supplier:
- ABM
- Gene target:
- TXNDC4
Related genes to: TXNDC4
- Gene:
- ERP44 NIH gene
- Name:
- endoplasmic reticulum protein 44
- Previous symbol:
- TXNDC4
- Synonyms:
- KIAA0573, PDIA10
- Chromosome:
- 9q31.1
- Locus Type:
- gene with protein product
- Date approved:
- 2002-11-11
- Date modifiied:
- 2018-11-15
Related products to: TXNDC4
Related articles to: TXNDC4
- Perilipins (PLINs) are lipid droplet-associated proteins that regulate lipid storage, mobilization, and metabolism, yet their roles in invertebrates remain poorly characterized. This study aimed to investigate the evolutionary conservation and functional adaptation of PLIN2 in the sea cucumber . Phylogenetic analysis placed PLIN2 within the PLIN2 clade, forming an echinoderm-specific branch distinct from vertebrate PLIN2s. Structural prediction revealed an N-terminal PAT domain containing an amphipathic helix that was required for lipid droplet targeting, as deletion of this region abolished its localization to lipid droplet. Functionally, PLIN2 abundance positively correlated with lipid droplet formation, and its knockdown reduced triacylglycerol accumulation while upregulating lipolysis-related genes. Pull-down and co-immunoprecipitation assays identified interactions between PLIN2 and the endoplasmic reticulum protein ERP44, as well as the mitochondrial protein TRXR2, suggesting a role in lipid droplet-organelle coupling. Consistently, disruption of the PLIN2-TRXR2 module impaired fatty acid transfer from lipid droplets to mitochondria, leading to suppressed β-oxidation and decreased ATP production. In addition, PLIN2 mediates the protective role of lipid droplets against -induced ER stress. Together, these findings establish PLIN2 as a multifunctional lipid droplet-associated protein that coordinates lipid droplet stability with organelle communication, energy metabolism, and ER homeostasis. - Source: PubMed
Publication date: 2026/05/28
Fan HongYu JintaoWang WenhaoLv ZhimengZhu SiLi Chenghua - Recent studies have revealed that exosomes, important regulators of intercellular communication, participate in various cardiac abnormalities, including hypertrophy. Cardiac fibroblasts (CFs) are one of the most abundant cell types of the heart. Exosomes secreted by CFs (CFs-Exo) have been proven to participate in myocardial ischemia and atrial fibrillation. However, the roles of CFs-Exo in cardiac hypertrophy and the underlying mechanism remain to be elucidated. Our study revealed that exosomes from isoproterenol (ISO)-stimulated CFs induced hypertrophic responses and activated the calcium signaling pathway in neonatal rat cardiomyocytes (CMs). The expression of microRNA-376c-3p (miR-376c-3p) was significantly increased in CFs following ISO stimulation; concomitantly, the contents of miR-376c-3p were also increased in their exosomes. The pro-hypertrophic effects of ISO-stimulated CFs could be attributed to the exosomal delivery of miR-376c-3p, which was subsequently absorbed by neonatal rat CMs and resulted in elevated cellular miR-376c-3p content. Furthermore, endoplasmic reticulum protein 44 was identified as a direct target of miR-376c-3p. MiR-376c-3p suppressed endoplasmic reticulum protein 44 in CMs to promote Ca release from the sarcoplasmic reticulum, leading to the activation of calcineurin/nuclear factors of activated T cells signaling and the subsequent onset of hypertrophy. Additionally, transfection of CFs with miR-376c-3p mimic upregulated miR-376c-3p in the derived exosomes. Administration of mimic upregulated miR-376c-3p in the derived exosomes provoked cardiac hypertrophy and impaired heart function in mice. In contrast, downregulation of miR-376c-3p in exosomes of CFs ameliorated the detrimental effects of exosomes on CMs. These results uncovered a new role of CFs-Exo in the pathogenesis of cardiac hypertrophy, suggesting a potential therapeutic strategy by counteracting exosomal miR-376c-3p. SIGNIFICANCE STATEMENT: Our data showed that the microRNA-376c-3p (miR-376c-3p) level was increased in isoproterenol-activated fibroblasts and secreted exosomes, which subsequently provoked hypertrophic responses via promoting Ca release from the sarcoplasmic reticulum in cardiomyocytes. The detrimental effects of miR-376c-3p could be attributed to the inhibition of the downstream target endoplasmic reticulum protein 44. These findings highlighted a novel mechanism of exosome-mediated pathological cardiac hypertrophy and suggested a promising therapeutic strategy by intervening in exosomal miR-376c-3p. - Source: PubMed
Publication date: 2026/05/14
Zhang YuexinHu XiaopeiLi JieJiang LujingHuang JunkaiZhang BingsenYe Jiantao - The biogenesis of secretory proteins proceeds under sequential quality control checkpoints operating along the exocytic pathway. Unlike other chaperones that reside primarily in the endoplasmic reticulum, ERp44 cycles through the Golgi to control the assembly of polymeric proteins and the localization of a few endoplasmic reticulum resident enzymes (ERAP1, Prx4, Ero1α, and SUMF1). To gain information about its pathophysiological role, we generated ERp44-deficient models. ERp44 KO mice are smaller than control siblings, and show skeletal malformations and delayed bone development, with reduced collagen deposition. Similar skeletal defects were also observed in ERp44 knocked down zebrafish embryos, supporting a conserved role for ERp44 in skeletal development. In cellular models, ERp44 downregulation dramatically affects collagen type 1 deposition, causing intracellular procollagen 1 accumulation. We thus conclude that the levels of ERp44 are crucial for efficient collagen deposition. - Source: PubMed
Publication date: 2026/04/16
Pannese MariaCanciani BarbaraCarnovali MartaDalla Torre MarcoGallucci GianpieroMangiavini LauraMariotti MassimoPanina-Bordignon PaolaVan't Hof RobSitia RobertoAnelli Tiziana - Zinc ions (Zn2+) are essential trace metal ions in the human body. Intracellular Zn2+ levels are tightly regulated by two metal transporter families: ZIPs, which mediate Zn2+ influx into the cytosol, and ZnTs, which export Zn2+ from the cytosol to the extracellular space or sequester it into the cellular organelles. Within cells, Zn2+ plays multiple roles, acting as a catalytic cofactor for numerous enzymes, stabilizing protein structures, and functioning as a second messenger in signal transduction. In addition, Zn2+ is involved in the transient regulation of enzymatic activities. Here, we review recent findings that reveal novel roles of Zn2+ in the structural and functional regulations of the molecular chaperone ERp44 and the cargo receptor ERGIC-53, both of which operate for protein quality control in the early secretory pathway. - Source: PubMed
Watanabe SatoshiInaba Kenji - Zinc homeostasis is crucial for various biological processes, including gene regulation, signal transduction, and proteostasis. ZIP7 is a membrane transporter that exports zinc ions (Zn) from the lumen of the endoplasmic reticulum (ER) to the cytosol, and its dysfunction causes ER stress, although the underlying mechanism remains unclear. Here, we show that ZIP7 inhibition increases the labile Zn concentration in the ER to micromolar levels, approximately 10 times higher than its steady-state level. Such abnormally high Zn concentrations disrupt the function and trafficking of the Zn-dependent chaperone ERp44 at the ER-Golgi interface. In vitro assays using recombinant proteins demonstrated that Zn inhibits the Ero1α-PDI oxidative system, and that ERp44 enhances this inhibitory effect. Consequently, the ER redox environment becomes more reducing, severely impairing the oxidative folding of key membrane receptors such as Notch1 and EGFR. These findings reveal the essential role of zinc homeostasis in redox-dependent proteostasis within the ER. - Source: PubMed
Publication date: 2026/04/22
Amagai YutaArai ChihiroYamamoto WakanaWatanabe SatoshiKowada ToshiyukiSitia RobertoHoseki JunMizukami ShinMatsumoto MasakiInaba Kenji