Abstract
The condensation and compartmentalization of biomacromolecules in the cell are driven by the process of phase separation. The main effectors of phase separation are intrinsically disordered proteins, which include proteins with a phenylalanine-glycine (FG) repeat domain. Our understanding of the biological function of FG repeat proteins during phase separation has been mainly derived from recent research on a member of the nuclear pore complex proteins, nucleoporins containing FG repeat domain (FG-NUPs). FG-NUPs form meshwork structures by inter- and intra-molecular FG domain interactions, which confine the nucleo-cytoplasmic exchange. Whereas FG-NUPs localize in the nuclear membrane, other FG repeat proteins reside in the cytoplasm and the nucleoplasm, and the biological function of the FG repeat domain of these proteins is not well described. In the present review, we list the FG repeat proteins that are known to phase separate in the cell, and review their biological functions. We extract the unraveled features of FG repeat proteins as an activator of barrier formation and homotypic cell-cell interactions. Understanding the regulatory mechanisms of FG repeat proteins will provide a potential delivery tool for therapeutic reagents.
Highlights
The phenomenon of phase separation in living organisms was first observed in the P granules of Caenorhabditis elegans (Brangwynne et al, 2009)
We aimed to discover novel FG repeat proteins, which might have essential roles in biological function other than forming nuclear pore
Previous studies have clarified the role of FG repeats in nuclear pores
Summary
The phenomenon of phase separation in living organisms was first observed in the P granules of Caenorhabditis elegans (Brangwynne et al, 2009). Liquid-liquid phase separation has been reported as a driving force for the formation of various membraneless organelles, such as nucleoli, stress granules, and microtubule organizing centers, leading to the reconsideration of various intracellular phenomena from the viewpoint of phase separation (Brangwynne et al, 2011; Molliex et al, 2015; Rale et al, 2018). Organelles with membranes, such as mitochondria and the endoplasmic reticulum, carry out efficient reactions via a series of internal functions by assembling proteins. Phase separation is involved in intracellular compartmentalization and enrichment, which provides the basis for the proper functioning of cells
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