Academic Journal
Phase separation of insulin receptor substrate 1 drives the formation of insulin/IGF-1 signalosomes
| العنوان: | Phase separation of insulin receptor substrate 1 drives the formation of insulin/IGF-1 signalosomes |
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| المؤلفون: | Gao, Xiu Kui, Rao, Xi Sheng, Cong, Xiao Xia, Sheng, Zu Kang, Sun, Yu Ting, Xu, Shui Bo, Wang, Jian Feng, Liang, Yong Heng, Lu, Lin Rong, Ouyang, Hongwei, Ge, Huiqing, Guo, Jian-sheng, Wu, Hang-jun, Sun, Qi Ming, Wu, Hao-bo, Bao, Zhang, Zheng, Li Ling, Zhou, Yi Ting |
| المصدر: | Cell Discovery ; volume 8, issue 1 ; ISSN 2056-5968 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2022 |
| الوصف: | As a critical node for insulin/IGF signaling, insulin receptor substrate 1 (IRS-1) is essential for metabolic regulation. A long and unstructured C-terminal region of IRS-1 recruits downstream effectors for promoting insulin/IGF signals. However, the underlying molecular basis for this remains elusive. Here, we found that the C-terminus of IRS-1 undergoes liquid-liquid phase separation (LLPS). Both electrostatic and hydrophobic interactions were seen to drive IRS-1 LLPS. Self-association of IRS-1, which was mainly mediated by the 301–600 region, drives IRS-1 LLPS to form insulin/IGF-1 signalosomes. Moreover, tyrosine residues of YXXM motifs, which recruit downstream effectors, also contributed to IRS-1 self-association and LLPS. Impairment of IRS-1 LLPS attenuated its positive effects on insulin/IGF-1 signaling. The metabolic disease-associated G972R mutation impaired the self-association and LLPS of IRS-1. Our findings delineate a mechanism in which LLPS of IRS-1-mediated signalosomes serves as an organizing center for insulin/IGF-1 signaling and implicate the role of aberrant IRS-1 LLPS in metabolic diseases. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1038/s41421-022-00426-x |
| الاتاحة: | http://dx.doi.org/10.1038/s41421-022-00426-x https://www.nature.com/articles/s41421-022-00426-x.pdf https://www.nature.com/articles/s41421-022-00426-x |
| Rights: | https://creativecommons.org/licenses/by/4.0 ; https://creativecommons.org/licenses/by/4.0 |
| رقم الانضمام: | edsbas.3BDFD0F |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41421-022-00426-x |
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