In addition, differing sets of those ligands are available in cell type- and context-dependent scenarios. In contrast, the GPI-anchored prion protein was shown to bind several extracellular and transmembrane ligands, which are required to endow that protein with the ability to play various roles in transmembrane signal transduction. Often each such process has been heralded as the bona fide function of PrP C, despite restricted attention paid to a selected phenotypic trait, associated with either modulation of gene expression or to the engagement of PrP C with a single ligand. Extensive experimental work disclosed multiple physiological roles of PrP C at the molecular, cellular and systemic levels, affecting the homeostasis of copper, neuroprotection, stem cell renewal and memory mechanisms, among others. PrP C is highly expressed in both the nervous and immune systems, as well as in other organs, but its functions are controversial. Misfolding of PrP C is associated with the transmissible spongiform encephalopathies (TSEs), whereas its normal conformer serves as a receptor for oligomers of the β-amyloid peptide, which play a major role in the pathogenesis of Alzheimer’s Disease (AD). The prion glycoprotein (PrP C) is mostly located at the cell surface, tethered to the plasma membrane through a glycosyl-phosphatydil inositol (GPI) anchor. Laboratory of Neurogenesis, Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.Similar methods could be employed for rational engineering of artificial organelles and other membraneless biocatalytic compartments. 'It may serve as a general biophysical approach for assembling scaffold-signaling complexes and regulating ACD. Zhao Wei, corresponding author of the study. 'The results revealed that phase separation modulates the assembly and dynamics of scaffold-signaling hubs in C. In living cells, SpmX was found to impede the cell-pole accumulation of PodJ and client recruitment, suggesting it may be involved in the new-to-old cell-pole remodeling. SpmX inhibited PodJ condensate formation and promoted PodJ condensate aging in vitro. Moreover, a negative regulation of PodJ phase separation by the old-cell-pole scaffold protein SpmX was observed. In addition, both of the phase separation-related domains were found to be involved in recruiting client signaling proteins, indicating that phase separation of PodJ functionally contributes to forming the PodJ–client complexes. Either the coiled-coil 4–6 region or the intrinsically disordered region in PodJ could mediate PodJ phase separation. PodJ formed biomolecular condensates both in vitro and in vivo. The researchers found that phase separation played an essential role in the C. crescentus cells with membraneless biomolecular condensates. In the pre-division cell stage, the polarization of new-pole signaling proteins by the scaffold PodJ coordinates to modulate the phosphorylation levels of a set of downstream signaling proteins, thus determining the cell fate of C. 23.Īs a well-established model for studying bacterial ACD, Caulobacter crescentus produces a motile swarmer cell and a sessile stalked cell during each cell cycle.

The study was published in Nature Communications on Nov. Zhao Wei from the Shenzhen Institute of Advanced Technology (SIAT) of the Chinese Academy of Sciences proposed that the polar organelle development scaffold protein PodJ in the new cell pole forms biomolecular condensates with physiological functions via phase separation, which help to establish and regulate the asymmetry of bacterial cells. However, the biomolecular basis and regulatory mechanism of the polar signaling complexes has been largely unclear. The polarization of the scaffold-signaling hubs at cell poles constitutes the basis of ACD.

Scaffold protein assembly