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Phospho‐regulation of intrinsically disordered proteins for actin assembly and endocytosis
Author(s) -
Miao Yansong,
Tipakornsaowapak Teepiyanut,
Zheng Liangzhen,
Mu Yuguang,
Lewellyn Eric
Publication year - 2018
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.14493
Subject(s) - endocytic cycle , endocytosis , microbiology and biotechnology , biology , membrane curvature , actin remodeling , actin , actin cytoskeleton , actin binding protein , clathrin , cytoskeleton , biochemistry , vesicle , membrane , receptor , cell
Actin filament assembly contributes to the endocytic pathway pleiotropically, with active roles in clathrin‐dependent and clathrin‐independent endocytosis as well as subsequent endosomal trafficking. Endocytosis comprises a series of dynamic events, including the initiation of membrane curvature, bud invagination, vesicle abscission and subsequent vesicular transport. The ultimate success of endocytosis requires the coordinated activities of proteins that trigger actin polymerization, recruit actin‐binding proteins ( ABP s) and organize endocytic proteins ( EP s) that promote membrane curvature through molecular crowding or scaffolding mechanisms. A particularly interesting phenomenon is that multiple EP s and ABP s contain a substantial percentage of intrinsically disordered regions ( IDR s), which can contribute to protein coacervation and phase separation. In addition, intrinsically disordered proteins (IDPs) frequently contain sites for post‐translational modifications (PTMs) such as phosphorylation, and these modifications exhibit a high preference for IDR residues [Groban ES et al . (2006) PL oS Comput Biol 2, e32]. PTMs are implicated in regulating protein function by modulating the protein conformation, protein–protein interactions and the transition between order and disorder states of IDPs. The molecular mechanisms by which IDR s of ABP s and EP s fine‐tune actin assembly and endocytosis remain mostly unexplored and elusive. In this review, we analyze protein sequences of budding yeast EP s and ABP s, and discuss the potential underlying mechanisms for regulating endocytosis and actin assembly through the emerging concept of IDR ‐mediated protein multivalency, coacervation, and phase transition, with an emphasis on the phospho‐regulation of IDR s. Finally, we summarize the current understanding of how these mechanisms coordinate actin cytoskeleton assembly and membrane curvature formation during endocytosis in budding yeast.