Phospho‐regulation of intrinsically disordered proteins for actin assembly and endocytosis

• Main Authors: Miao, Yansong, Tipakornsaowapak, Teepiyanut, Zheng, Liangzhen, Mu, Yuguang, Lewellyn, Eric
• Other Authors: School of Chemical and Biomedical Engineering
• Format: Article
• Language: English
• Published: 2020
• Subjects: Science::Biological sciences; Actin Cytoskeleton; Endocytosis
• Online Access: https://hdl.handle.net/10356/137135
• Institution: Nanyang Technological University

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 (ABPs) and organize endocytic proteins (EPs) that promote membrane curvature through molecular crowding or scaffolding mechanisms. A particularly interesting phenomenon is that multiple EPs and ABPs contain a substantial percentage of intrinsically disordered regions (IDRs), 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) PLoS 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 IDRs of ABPs and EPs fine‐tune actin assembly and endocytosis remain mostly unexplored and elusive. In this review, we analyze protein sequences of budding yeast EPs and ABPs, 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 IDRs. Finally, we summarize the current understanding of how these mechanisms coordinate actin cytoskeleton assembly and membrane curvature formation during endocytosis in budding yeast.