Lee Chaeyeon, Yu Jeonghye, Shin Jongpil, Yu Jihwan, Heo Yungyeong, Lee Moosung, Yu Daseuli, Park YongKeun, Heo Won Do
Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea.
Department of Physics, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, South Korea.
Nat Commun. 2025 Jul 7;16(1):6230. doi: 10.1038/s41467-025-61322-y.
Cells compartmentalize biomolecules in membraneless structures called biomolecular condensates. While their roles in regulating cellular processes are increasingly understood, tools for their synthetic manipulation remain limited. Here, we introduce RELISR (Reversible Light-Induced Store and Release), an optogenetic condensate system that enables reversible storage and release of proteins or mRNAs. RELISR integrates multivalent scaffolds, optogenetic switches, and cargo-binding domains to trap cargo in the dark and release it upon blue-light exposure. We demonstrate its utility in primary neurons and show that light-triggered release of signaling proteins can modulate fibroblast morphology. Furthermore, light-induced release of cargo mRNA results in protein translation both in vitro and in live mice. RELISR thus provides a versatile platform for spatiotemporal control of protein activity and mRNA translation in complex biological systems, with broad potential for research and therapeutic applications.
细胞将生物分子分隔在称为生物分子凝聚物的无膜结构中。虽然它们在调节细胞过程中的作用越来越被人们所了解，但用于对其进行合成操控的工具仍然有限。在此，我们介绍了RELISR（可逆光诱导存储与释放），这是一种光遗传学凝聚物系统，能够实现蛋白质或mRNA的可逆存储与释放。RELISR整合了多价支架、光遗传学开关和货物结合结构域，以便在黑暗中捕获货物，并在蓝光照射时释放货物。我们展示了它在原代神经元中的效用，并表明信号蛋白的光触发释放可以调节成纤维细胞形态。此外，货物mRNA的光诱导释放在体外和活体小鼠中均导致蛋白质翻译。因此，RELISR为在复杂生物系统中对蛋白质活性和mRNA翻译进行时空控制提供了一个通用平台，在研究和治疗应用方面具有广阔的潜力。
