Insulated Switches: Dual-Function Protein RalGEFRGL-1 Promotes Developmental Fidelity
| العنوان: | Insulated Switches: Dual-Function Protein RalGEFRGL-1 Promotes Developmental Fidelity |
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| المؤلفون: | David J. Reiner, Tam Duong, Neal R Rasmussen |
| المصدر: | International Journal of Molecular Sciences, Vol 21, Iss 7610, p 7610 (2020) International Journal of Molecular Sciences |
| بيانات النشر: | MDPI AG, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | DAF-18 LET-23, PTEN, Cell, toggle, Models, Biological, PI3K, Catalysis, Vulva, Inorganic Chemistry, DSL, lcsh:Chemistry, LIN-3, Phosphatidylinositol 3-Kinases, Precursor cell, medicine, Animals, Cell Lineage, Physical and Theoretical Chemistry, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Molecular Biology, lcsh:QH301-705.5, Spectroscopy, PI3K/AKT/mTOR pathway, Dual function, PI3 Kinase, biology, Effector, Developmental induction, Organic Chemistry, Gene Expression Regulation, Developmental, General Medicine, Computer Science Applications, Cell biology, bifunctional, medicine.anatomical_structure, lcsh:Biology (General), lcsh:QD1-999, Perspective, network, biology.protein, ras Proteins, Female, ral GTP-Binding Proteins, Developmental biology, Proto-Oncogene Proteins c-akt, Signal Transduction |
| الوصف: | The C. elegans vulva is an excellent model for the study of developmental biology and cell–cell signaling. The developmental induction of vulval precursor cells (VPCs) to assume the 3°-3°-2°-1°-2°-3° patterning of cell fates occurs with 99.8% accuracy. During C. elegans vulval development, an EGF signal from the anchor cell initiates the activation of RasLET-60 > RafLIN-45 > MEKMEK-2 > ERKMPK-1 signaling cascade to induce the 1° cell. The presumptive 1° cell signals its two neighboring cells via NotchLIN-12 to develop 2° cells. In addition, RasLET-60 switches effectors to RalGEFRGL-1 > RalRAL-1 to promote 2° fate. Shin et al. (2019) showed that RalGEFRGL-1 is a dual-function protein in VPCs fate patterning. RalGEFRGL-1 functions as a scaffold for PDKPDK-1 > AktAKT-1/2 modulatory signaling to promote 1° fate in addition to propagating the RasLET-60 modulatory signal through RalRAL-1 to promote 2° fate. The deletion of RalGEFRGL-1 increases the frequency of VPC patterning errors 15-fold compared to the wild-type control. We speculate that RalGEFRGL-1 represents an “insulated switch”, whereby the promotion of one signaling activity curtails the promotion of the opposing activity. This property might increase the impact of the switch on fidelity more than two separately encoded proteins could. Understanding how developmental fidelity is controlled will help us to better understand the origins of cancer and birth defects, which occur in part due to the misspecification of cell fates. |
| اللغة: | English |
| تدمد: | 1661-6596 1422-0067 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::65e1c937d30fcaa583bc58d32918a233Test https://www.mdpi.com/1422-0067/21/20/7610Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....65e1c937d30fcaa583bc58d32918a233 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 16616596 14220067 |
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