An Autocrine Negative Feedback Loop Inhibits Dictyostelium discoideum Proliferation through Pathways Including IP3/Ca 2+
| Autor: | Louis A. Cadena, Jacquelyn R. McCullough, David E. Zimmerhanzel, Richard H. Gomer, Ramesh Rijal, Yu Tang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
inositol trisphosphate
G protein Protozoan Proteins Inositol 1 4 5-Trisphosphate calcium signaling Microbiology Dictyostelium discoideum 03 medical and health sciences chemistry.chemical_compound Polyphosphate kinase 0302 clinical medicine GTP-Binding Proteins Polyphosphates Virology Tensin Dictyostelium Small GTPase 030304 developmental biology 0303 health sciences PLC/IP3/Ca2+ biology Phospholipase C Chemistry quorum sensing polyphosphate Inositol trisphosphate Editor's Pick biology.organism_classification QR1-502 Cell biology cell proliferation 030220 oncology & carcinogenesis cell density sensing Calcium Signal transduction Research Article Signal Transduction |
| Zdroj: | mBio, Vol 12, Iss 3 (2021) mBio |
| ISSN: | 2150-7511 |
| DOI: | 10.1128/mBio.01347-21 |
| Popis: | Little is known about how eukaryotic cells can sense their number or spatial density and stop proliferating when the local density reaches a set value. We previously found that Dictyostelium discoideum accumulates extracellular polyphosphate to inhibit its proliferation, and this requires the G protein-coupled receptor GrlD and the small GTPase RasC. Here, we show that cells lacking the G protein component Gβ, the Ras guanine nucleotide exchange factor GefA, phosphatase and tensin homolog (PTEN), phospholipase C (PLC), inositol 1,4,5-trisphosphate (IP3) receptor-like protein A (IplA), polyphosphate kinase 1 (Ppk1), or the TOR complex 2 component PiaA have significantly reduced sensitivity to polyphosphate-induced proliferation inhibition. Polyphosphate upregulates IP3, and this requires GrlD, GefA, PTEN, PLC, and PiaA. Polyphosphate also upregulates cytosolic Ca2+, and this requires GrlD, Gβ, GefA, RasC, PLC, IplA, Ppk1, and PiaA. Together, these data suggest that polyphosphate uses signal transduction pathways including IP3/Ca2+ to inhibit the proliferation of D. discoideum. IMPORTANCE Many mammalian tissues such as the liver have the remarkable ability to regulate their size and have their cells stop proliferating when the tissue reaches the correct size. One possible mechanism involves the cells secreting a signal that they all sense, and a high level of the signal tells the cells that there are enough of them and to stop proliferating. Although regulating such mechanisms could be useful to regulate tissue size to control cancer or birth defects, little is known about such systems. Here, we use a microbial system to study such a mechanism, and we find that key elements of the mechanism have similarities to human proteins. This then suggests the possibility that we may eventually be able to regulate the proliferation of selected cell types in humans and animals. |
| Databáze: | OpenAIRE |
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