摘要
Evolution has enabled living cells to adopt their structural and functional complexity by organizing intricate cellular compartments,such as membrane-bound and membraneless organelles(MLOs),for spatiotemporal catalysis of physiochemical reactions essential for cell plasticity control.Emerging evidence and view support the notion that MLOs are built by multivalent interactions of biomolecules via phase separation and transition mechanisms.In healthy cells,dynamic chemical modifications regulate MLO plasticity,and reversible phase separation is essential for cell homeostasis.Emerging evidence revealed that aberrant phase separation results in numerous neurodegenerative disorders,cancer,and other diseases.In this review,we provide molecular underpinnings on(i)mechanistic understanding of phase separation,(ii)unifying structural and mechanistic principles that underlie this phenomenon,(iii)various mechanisms that are used by cells for the regulation of phase separation,and(iv)emerging therapeutic and other applications.
基金
supported in part by grants from the National Natural Science Foundation of China(32090040,31621002,21922706,81630080,31430054,91854203,91853115,and 31671405)
the National Key Research and Development Program of China(2017YFA0503600 and 2016YFA0100500)
the Ministry of Education of China(IRT_17R102)
the Strategic Priority Research Program of Chinese Academy of Sciences(XDB19000000)
the Fundamental Research Funds for the Central Universities(KB2070000023 and WK2070000194)
National Institutes of Health Grants(CA164133,DK115812,and DK56292)
We thank our laboratory members for stimulating discussion。
