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18 pages, 8381 KiB

Open AccessArticle

Inhibition of PIKfyve Leads to Lysosomal Disorders via Dysregulation of mTOR Signaling

by Jianhong Xia, Haiyun Wang, Zhihang Zhong and Jun Jiang

Cells 2024, 13(11), 953; https://doi.org/10.3390/cells13110953 - 30 May 2024

Cited by 1 | Viewed by 2219

PIKfyve is an endosomal lipid kinase that synthesizes phosphatidylinositol 3,5-biphosphate from phosphatidylinositol 3-phsphate. Inhibition of PIKfyve activity leads to lysosomal enlargement and cytoplasmic vacuolation, attributed to impaired lysosomal fission processes and homeostasis. However, the precise molecular mechanisms underlying these effects remain a topic of debate. In this study, we present findings from PIKfyve-deficient zebrafish embryos, revealing enlarged macrophages with giant vacuoles reminiscent of lysosomal storage disorders. Treatment with mTOR inhibitors or effective knockout of mTOR partially reverses these abnormalities and extend the lifespan of mutant larvae. Further in vivo and in vitro mechanistic investigations provide evidence that PIKfyve activity is essential for mTOR shutdown during early zebrafish development and in cells cultured under serum-deprived conditions. These findings underscore the critical role of PIKfyve activity in regulating mTOR signaling and suggest potential therapeutic applications of PIKfyve inhibitors for the treatment of lysosomal storage disorders. Full article

(This article belongs to the Topic Application of Animal Models: From Physiology to Pathology)

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20 pages, 7514 KiB

Open AccessArticle

BSA-Seq and Transcriptomic Analysis Provide Candidate Genes Associated with Inflorescence Architecture and Kernel Orientation by Phytohormone Homeostasis in Maize

by Yang Wang, Yang Li, Wenjie Zhang, Yue Yang, Yuting Ma, Xinyang Li, Dexuan Meng, Haishan Luo, Wei Xue, Xiangling Lv, Fenghai Li, Wanli Du and Xiaolin Geng

Int. J. Mol. Sci. 2023, 24(13), 10728; https://doi.org/10.3390/ijms241310728 - 27 Jun 2023

Cited by 5 | Viewed by 2366

Abstract

The developmental plasticity of the maize inflorescence depends on meristems, which directly affect reproductive potential and yield. However, the molecular roles of upper floral meristem (UFM) and lower floral meristem (LFM) in inflorescence and kernel development have not been fully elucidated. In this study, we characterized the reversed kernel1 (rk1) novel mutant, which contains kernels with giant embryos but shows normal vegetative growth like the wild type (WT). Total RNA was extracted from the inflorescence at three stages for transcriptomic analysis. A total of 250.16-Gb clean reads were generated, and 26,248 unigenes were assembled and annotated. Gene ontology analyses of differentially expressed genes (DEGs) detected in the sexual organ formation stage revealed that cell differentiation, organ development, phytohormonal responses and carbohydrate metabolism were enriched. The DEGs associated with the regulation of phytohormone levels and signaling were mainly expressed, including auxin (IAA), jasmonic acid (JA), gibberellins (GA), and abscisic acid (ABA). The transcriptome, hormone evaluation and immunohistochemistry observation revealed that phytohormone homeostasis were affected in rk1. BSA-Seq and transcriptomic analysis also provide candidate genes to regulate UFM and LFM development. These results provide novel insights for understanding the regulatory mechanism of UFM and LFM development in maize and other plants. Full article

(This article belongs to the Special Issue Phytohormones: Important Participators in Plant Growth and Development)

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21 pages, 2137 KiB

Open AccessArticle

Targeted Disruption of the MORG1 Gene in Mice Causes Embryonic Resorption in Early Phase of Development

by Sophie Wulf, Luisa Mizko, Karl-Heinz Herrmann, Marta Sánchez-Carbonell, Anja Urbach, Cornelius Lemke, Alexander Berndt, Ivonne Loeffler and Gunter Wolf

Biomolecules 2023, 13(7), 1037; https://doi.org/10.3390/biom13071037 - 24 Jun 2023

Cited by 1 | Viewed by 2440

Abstract

The mitogen-activated protein kinase organizer 1 (MORG1) is a scaffold molecule for the ERK signaling pathway, but also binds to prolyl-hydroxylase 3 and modulates HIFα expression. To obtain further insight into the role of MORG1, knockout-mice were generated by homologous recombination. While Morg1+/− mice developed normally without any apparent phenotype, there were no live-born Morg1−/− knockout offspring, indicating embryonic lethality. The intrauterine death of Morg1−/− embryos is caused by a severe failure to develop brain and other neuronal structures such as the spinal cord and a failure of chorioallantoic fusion. On E8.5, Morg1−/− embryos showed severe underdevelopment and proliferative arrest as indicated by absence of Ki67 expression, impaired placental vascularization and altered phenotype of trophoblast giant cells. On E9.5, the malformed Morg1−/− embryos showed defective turning into the final fetal position and widespread apoptosis in many structures. In the subsequent days, apoptosis and decomposition of embryonic tissue progressed, accompanied by a massive infiltration of inflammatory cells. Developmental aberrancies were accompanied by altered expression of HIF-1/2α and VEGF-A and caspase-3 activation in embryos and extraembryonic tissues. In conclusion, the results suggest a multifactorial process that causes embryonic death in homozygous Morg1 mutant mice, described here, to the best of our knowledge, for the first time. Full article

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13 pages, 232 KiB

Open AccessArticle

Effect of Instant Cooked Giant Embryonic Rice on Body Fat Weight and Plasma Lipid Profile in High Fat-Fed Mice

by Soo Im Chung, Tae Hyeong Kim, Catherine W. Rico and Mi Young Kang

Nutrients 2014, 6(6), 2266-2278; https://doi.org/10.3390/nu6062266 - 13 Jun 2014

Cited by 12 | Viewed by 7971

Abstract

The comparative effects of instant cooked rice made from giant embryo mutant or ordinary normal rice on body weight and lipid profile in high fat-fed mice were investigated. The animals were given experimental diets for seven weeks: normal control (NC), high fat (HF), and HF supplemented with instant normal white (HF-NW), normal brown (HF-NB), giant embryonic white (HF-GW), or giant embryonic brown (HF-GB) rice. The HF group showed markedly higher body weight, body fat, plasma and hepatic triglyceride and cholesterol concentrations, and atherogenic index relative to NC group. However, instant rice supplementation counteracted this high fat-induced hyperlipidemia through regulation of lipogenesis and adipokine production. The GB rice exhibited greater hypolipidemic and body fat-lowering effects than the GW or NB rice. These findings illustrate that the giant embryo mutant may be useful as functional biomaterial for the development of instant rice with strong preventive action against high fat diet-induced hyperlipidemia and obesity. Full article

(This article belongs to the Special Issue Nutrient Fortification and Human Health)

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