Synthetic receptor scaffolds significantly affect the efficiency of cell fate signals
Abstract Mimicry of receptor functions by designing synthetic receptors would be one of the recently hot research trends in cell engineering. While several types of synthetic receptors have been designed to induce desired cell fates in response to external stimuli, little is known about which recept...
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2024-03-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-024-56612-2 |
| _version_ | 1797266823067992064 |
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| author | Kirato Umene Masahiro Kawahara |
| author_facet | Kirato Umene Masahiro Kawahara |
| author_sort | Kirato Umene |
| collection | DOAJ |
| description | Abstract Mimicry of receptor functions by designing synthetic receptors would be one of the recently hot research trends in cell engineering. While several types of synthetic receptors have been designed to induce desired cell fates in response to external stimuli, little is known about which receptor type signals more efficiently for inducing a certain cell fate. In this study, we compared the performance of three types of synthetic receptor scaffolds, i.e. myristoylated, cytosolic, and transmembrane types that signal through JAK-dependent phosphorylation of tyrosine motifs to transduce growth signaling. As a result, the phosphorylation levels of JAK and subsequent downstream signaling molecules were significantly maintained in the cytosolic type receptors, leading to more efficient cell growth than the other types. In contrast, the phosphorylation levels of JAK decreased in a motif-dependent manner in the transmembrane type receptors. Although various studies on receptor engineering based on domain or motif engineering have been reported, to our knowledge this study is the first to demonstrate that synthetic receptor scaffolds significantly affect the efficiency of cell fate signals. These findings are important for both receptor biology and receptor engineering, providing guidelines for rationally designing synthetic receptors that can transduce as efficient signaling as possible. |
| first_indexed | 2024-04-25T01:06:48Z |
| format | Article |
| id | doaj.art-22501eef96744147991ee6fd4311d448 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-25T01:06:48Z |
| publishDate | 2024-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-22501eef96744147991ee6fd4311d4482024-03-10T12:10:57ZengNature PortfolioScientific Reports2045-23222024-03-011411810.1038/s41598-024-56612-2Synthetic receptor scaffolds significantly affect the efficiency of cell fate signalsKirato Umene0Masahiro Kawahara1Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of TokyoDepartment of Chemistry and Biotechnology, Graduate School of Engineering, The University of TokyoAbstract Mimicry of receptor functions by designing synthetic receptors would be one of the recently hot research trends in cell engineering. While several types of synthetic receptors have been designed to induce desired cell fates in response to external stimuli, little is known about which receptor type signals more efficiently for inducing a certain cell fate. In this study, we compared the performance of three types of synthetic receptor scaffolds, i.e. myristoylated, cytosolic, and transmembrane types that signal through JAK-dependent phosphorylation of tyrosine motifs to transduce growth signaling. As a result, the phosphorylation levels of JAK and subsequent downstream signaling molecules were significantly maintained in the cytosolic type receptors, leading to more efficient cell growth than the other types. In contrast, the phosphorylation levels of JAK decreased in a motif-dependent manner in the transmembrane type receptors. Although various studies on receptor engineering based on domain or motif engineering have been reported, to our knowledge this study is the first to demonstrate that synthetic receptor scaffolds significantly affect the efficiency of cell fate signals. These findings are important for both receptor biology and receptor engineering, providing guidelines for rationally designing synthetic receptors that can transduce as efficient signaling as possible.https://doi.org/10.1038/s41598-024-56612-2 |
| spellingShingle | Kirato Umene Masahiro Kawahara Synthetic receptor scaffolds significantly affect the efficiency of cell fate signals Scientific Reports |
| title | Synthetic receptor scaffolds significantly affect the efficiency of cell fate signals |
| title_full | Synthetic receptor scaffolds significantly affect the efficiency of cell fate signals |
| title_fullStr | Synthetic receptor scaffolds significantly affect the efficiency of cell fate signals |
| title_full_unstemmed | Synthetic receptor scaffolds significantly affect the efficiency of cell fate signals |
| title_short | Synthetic receptor scaffolds significantly affect the efficiency of cell fate signals |
| title_sort | synthetic receptor scaffolds significantly affect the efficiency of cell fate signals |
| url | https://doi.org/10.1038/s41598-024-56612-2 |
| work_keys_str_mv | AT kiratoumene syntheticreceptorscaffoldssignificantlyaffecttheefficiencyofcellfatesignals AT masahirokawahara syntheticreceptorscaffoldssignificantlyaffecttheefficiencyofcellfatesignals |