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Membrane-Less Organelles: A Modern Understanding of the Organization and Functioning of the Intracellular Space

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biophysics".

Deadline for manuscript submissions: closed (31 March 2021) | Viewed by 19104

Special Issue Editors


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Guest Editor
Laboratory of Structural Dynamics, Stability and Folding of Proteins, Institute of Cytology, Russian Academy of Sciences, 4 Tikhoretsky Ave., 194064 St. Petersburg, Russia
Interests: protein structure, conformation and dynamics; globule and intrinsically disordered proteins; macromolecular crowding; membraneless organelles; protein aggregates; amyloid fibrils formation and structure; biosensors; biomarkers on the basis of fluorescent proteins and phytochromes; photophysics of fluorescent dyes; molecular rotors; intrinsic fluorescence of proteins; spectrofluorimetry device development
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
Laboratory of Structural Dynamics, Stability and Folding of Proteins, Institute of Cytology, Russian Academy of Sciences, 4 Tikhoretsky Ave., 194064 St. Petersburg, Russia
Interests: protein structure, conformation and dynamics; globule and intrinsically disordered proteins; macromolecular crowding; protein aggregates; liquid-liquid phase separation; membraneless organelles; photobodies, phytochromes
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
Laboratory of Structural Dynamics, Stability and Folding of Proteins, Institute of Cytology, Russian Academy of Sciences, 4 Tikhoretsky Ave., 194064 St. Petersburg, Russia
Interests: amyloid fibrils; thioflafin T fluorescence; equilibrium microdialysis; globule and intrinsically disordered proteins; proteins aggregattion; macromolecular crowding; membraneless organelles
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

According to the current knowledge in modern cellular biology, membrane-less organelles play an important role in the organization of various intracellular processes. These dynamic structures are formed and disassembled as a result of reversible liquid–liquid phase transitions that are highly controlled in biological systems. The fact that the cytoplasm and nucleus of cells, along with the “traditional” organelles that have membranes, separating their interior from the outside environment, contain various bodies (droplets) that do not have a membrane has been known for a long time. However, only in recent years  has attention has been drawn to the fact that, despite seemingly great differences in composition, localization, size, functions, etc., membrane-less organelles have many common features. Membrane-less organelles arise due to the phase separation of boipolymers under appropriate conditions, and the decisive role in this prosess is played by intrinsically disordered proteins. Membrane-less organelles provide an important means of carrying out fine cellular organization and the regulation of various intracellular processes. The abnormal functioning of membrane-less organelles is often accompanied by the formation of amyloid fibrils. This opens up new approaches to studying the processes of fibrillogenesis and cell aging.

This Special Issue aims to collect original and review papers on membrane-less organelles. It is a study of the following: their mechanisms of functioning, their structure of during normal cell function; diseases and aging; the identification of factors that regulate changes in the activity and structure of membrane-less organelles; as well as any other studies related to this topic.

You may choose our Joint Special Issue in Life.

Prof. Dr. Konstantin K. Turoverov
Dr. Alexander V. Fonin
Dr. Irina M. Kuznetsova
Guest Editors

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Keywords

  • intrinsically disordered protein
  • proteins post-translational modifications
  • crowding
  • liquid–liquid phase transition
  • membrane-less organelles
  • liquid-gel phase transition
  • amyloid fibrills
  • aggregates of amyloid fibrills
  • neurodegenerative diseases
  • cancer
  • aging
  • membrane-less organelles as a target for therapy in diseases

Published Papers (2 papers)

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Research

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18 pages, 2156 KiB  
Article
The Role of Non-Specific Interactions in Canonical and ALT-Associated PML-Bodies Formation and Dynamics
by Alexander V. Fonin, Sergey A. Silonov, Olesya G. Shpironok, Iuliia A. Antifeeva, Alexey V. Petukhov, Anna E. Romanovich, Irina M. Kuznetsova, Vladimir N. Uversky and Konstantin K. Turoverov
Int. J. Mol. Sci. 2021, 22(11), 5821; https://doi.org/10.3390/ijms22115821 - 29 May 2021
Cited by 16 | Viewed by 3022
Abstract
In this work, we put forward a hypothesis about the decisive role of multivalent nonspecific interactions in the early stages of PML body formation. Our analysis of the PML isoform sequences showed that some of the PML isoforms, primarily PML-II, are prone to [...] Read more.
In this work, we put forward a hypothesis about the decisive role of multivalent nonspecific interactions in the early stages of PML body formation. Our analysis of the PML isoform sequences showed that some of the PML isoforms, primarily PML-II, are prone to phase separation due to their polyampholytic properties and the disordered structure of their C-terminal domains. The similarity of the charge properties of the C-terminal domains of PML-II and PML-VI isoforms made it possible for the first time to detect migration of PML-VI from PML bodies to the periphery of the cell nucleus, similar to the migration of PML-II isoforms. We found a population of “small” (area less than 1 µm2) spherical PML bodies with high dynamics of PML isoforms exchange with nucleoplasm and a low fraction of immobilized proteins, which indicates their liquid state properties. Such structures can act as “seeds” of functionally active PML bodies, providing the necessary concentration of PML isoforms for the formation of intermolecular disulfide bonds between PML monomers. FRAP analysis of larger bodies of toroidal topology showed the existence of an insoluble scaffold in their structure. The hypothesis about the role of nonspecific multiple weak interactions in the formation of PML bodies is further supported by the change in the composition of the scaffold proteins of PML bodies, but not their solidification, under conditions of induction of dimerization of PML isoforms under oxidative stress. Using the colocalization of ALT-associated PML bodies (APBs) with TRF1, we identified APBs and showed the difference in the dynamic properties of APBs and canonical PML bodies. Full article
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20 pages, 2623 KiB  
Review
Liquid–Liquid Phase Separation in Crowded Environments
by Alain A. M. André and Evan Spruijt
Int. J. Mol. Sci. 2020, 21(16), 5908; https://doi.org/10.3390/ijms21165908 - 17 Aug 2020
Cited by 130 | Viewed by 15105
Abstract
Biomolecular condensates play a key role in organizing cellular fluids such as the cytoplasm and nucleoplasm. Most of these non-membranous organelles show liquid-like properties both in cells and when studied in vitro through liquid–liquid phase separation (LLPS) of purified proteins. In general, LLPS [...] Read more.
Biomolecular condensates play a key role in organizing cellular fluids such as the cytoplasm and nucleoplasm. Most of these non-membranous organelles show liquid-like properties both in cells and when studied in vitro through liquid–liquid phase separation (LLPS) of purified proteins. In general, LLPS of proteins is known to be sensitive to variations in pH, temperature and ionic strength, but the role of crowding remains underappreciated. Several decades of research have shown that macromolecular crowding can have profound effects on protein interactions, folding and aggregation, and it must, by extension, also impact LLPS. However, the precise role of crowding in LLPS is far from trivial, as most condensate components have a disordered nature and exhibit multiple weak attractive interactions. Here, we discuss which factors determine the scope of LLPS in crowded environments, and we review the evidence for the impact of macromolecular crowding on phase boundaries, partitioning behavior and condensate properties. Based on a comparison of both in vivo and in vitro LLPS studies, we propose that phase separation in cells does not solely rely on attractive interactions, but shows important similarities to segregative phase separation. Full article
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