Protein-protein interaction network controlling establishment and maintenance of switchable cell polarity
| Autor: | Luis António Menezes Carreira, Filipe Tostevin, Ulrich Gerland, Lotte Søgaard-Andersen |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Proteomics
Cancer Research Intravital Microscopy Hydrolases QH426-470 Biochemistry Protein protein interaction network Signaling Molecules Mathematical and Statistical Techniques Fluorescence Microscopy 0302 clinical medicine Cell Signaling Cell polarity Image Processing Computer-Assisted Guanine Nucleotide Exchange Factors Small GTPase Cell Cycle and Cell Division Protein Interaction Maps Myxococcus xanthus Genetics (clinical) Microscopy 0303 health sciences Mathematical Models Chemotaxis GTPase-Activating Proteins Cell Polarity Light Microscopy Enzymes Cell biology Cell Processes Protein Interaction Networks Guanine nucleotide exchange factor Network Analysis Research Article Signal Transduction Cell Physiology Computer and Information Sciences Imaging Techniques Motility Biology Research and Analysis Methods Network topology Models Biological 03 medical and health sciences Bacterial Proteins Fluorescence Imaging Genetics Molecular Biology Ecology Evolution Behavior and Systematics 030304 developmental biology Data Science Biology and Life Sciences Proteins Cell Biology biology.organism_classification Guanosine Triphosphatase Microscopy Fluorescence Enzymology 030217 neurology & neurosurgery |
| Zdroj: | PLoS Genetics PLoS Genetics, Vol 16, Iss 6, p e1008877 (2020) |
| ISSN: | 1553-7404 |
| DOI: | 10.1371/journal.pgen.1008877 |
| Popis: | Cell polarity underlies key processes in all cells, including growth, differentiation and division. In the bacterium Myxococcus xanthus, front-rear polarity is crucial for motility. Notably, this polarity can be inverted, independent of the cell-cycle, by chemotactic signaling. However, a precise understanding of the protein network that establishes polarity and allows for its inversion has remained elusive. Here, we use a combination of quantitative experiments and data-driven theory to unravel the complex interplay between the three key components of the M. xanthus polarity module. By studying each of these components in isolation and their effects as we systematically reconstruct the system, we deduce the network of effective interactions between the polarity proteins. RomR lies at the root of this network, promoting polar localization of the other components, while polarity arises from interconnected negative and positive feedbacks mediated by the small GTPase MglA and its cognate GAP MglB, respectively. We rationalize this network topology as operating as a spatial toggle switch, providing stable polarity for persistent cell movement whilst remaining responsive to chemotactic signaling and thus capable of polarity inversions. Our results have implications not only for the understanding of polarity and motility in M. xanthus but also, more broadly, for dynamic cell polarity. Author summary The asymmetric localization of cellular components (polarity) is at the core of many important cellular functions including growth, division, differentiation and motility. However, important questions still remain regarding the design principles underlying polarity networks and how their activity can be controlled in space and time. We use the rod-shaped bacterium Myxococcus xanthus as a model to study polarity and its regulation. Like many bacteria, in M. xanthus a well-defined front-rear polarity axis enables efficient translocation. This polarity axis is defined by asymmetric polar localization of a switch-like GTPase and its cognate regulators, and can be reversed in response to signaling cues. Here we use a combination of quantitative experiments and data-driven theory to deduce the network of interactions among the M. xanthus polarity proteins and to show how the combination of positive- and negative-feedback interactions give rise to asymmetric polar protein localization. We rationalize this network topology as operating as a spatial toggle switch, providing stable polarity for persistent cell movement whilst remaining responsive to chemotactic signaling and capable of polarity inversions. Our results have broader implications for our understanding of dynamic cell polarity and GTPase regulation in both bacteria and eukaryotic cells. |
| Databáze: | OpenAIRE |
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