scholarly journals A Novel Lens for Cell Volume Regulation: Liquid-Liquid Phase Separation

2021 ◽  
Vol 55 (S1) ◽  
pp. 135-160
Keyword(s):  
Phase Separation ◽  
Cell Membrane ◽  
Cell Volume ◽  
Volume Change ◽  
Cell Biology ◽  
Cell Volume Regulation ◽  
Organic Osmolytes ◽  
Regulatory Systems ◽  
Osmotic Water ◽  
Intracellular Changes

Cells are constantly exposed to the risk of volume perturbation under physiological conditions. The increase or decrease in cell volume accompanies intracellular changes in cell membrane tension, ionic strength/concentration and macromolecular crowding. To avoid deleterious consequences caused by cell volume perturbation, cells have volume recovery systems that regulate osmotic water flow by transporting ions and organic osmolytes across the cell membrane. Thus far, a number of biomolecules have been reported to regulate cell volume. However, the question of how cells sense volume change and modulate volume regulatory systems is not fully understood. Recently, the existence and significance of phaseseparated biomolecular condensates have been revealed in numerous physiological events, including cell volume perturbation. In this review, we summarize the current understanding of cell volume-sensing mechanisms, introduce recent studies on biomolecular condensates induced by cell volume change and discuss how biomolecular condensates contribute to cell volume sensing and cell volume maintenance. In addition to previous studies of biochemistry, molecular biology and cell biology, a phase separation perspective will allow us to understand the complicated volume regulatory systems of cells.

Cellular volume homeostasis

2004 ◽  
Vol 28 (4) ◽  
pp. 155-159 ◽  
Author(s):  
Kevin Strange
Keyword(s):  
Cell Volume ◽  
Metabolic Pathways ◽  
Cell Volume Regulation ◽  
Inorganic Ions ◽  
Organic Osmolytes ◽  
Solute Content ◽  
Signaling Mechanisms ◽  
Cellular Volume ◽  
Osmotic Water

All cells face constant challenges to their volume either through changes in intracellular solute content or extracellular osmolality. Cells respond to volume perturbations by activating membrane transport and/or metabolic processes that result in net solute loss or gain and return of cell volume to its normal resting state. This paper provides a brief overview of fundamental concepts of osmotic water flow across cell membranes, mechanisms of cell volume perturbation, the role of inorganic ions and organic osmolytes in cell volume regulation and the signaling mechanisms that regulate the activity of cell volume-sensitive transport and metabolic pathways.

scholarly journals Multivalent proteins rapidly and reversibly phase-separate upon osmotic cell volume change

2019 ◽  
Author(s):  
Ameya P. Jalihal ◽  
Sethuramasundaram Pitchiaya ◽  
Lanbo Xiao ◽  
Pushpinder Bawa ◽  
Xia Jiang ◽  
...  
Keyword(s):  
Phase Separation ◽  
Cell Volume ◽  
Volume Change ◽  
Mammalian Cells ◽  
Internal State ◽  
Transcription Termination ◽  
Cell Types ◽  
List Type ◽  
Molecular Crowding ◽  
Minimal Impact

SUMMARYProcessing bodies (PBs) and stress granules (SGs) are prominent examples of sub-cellular, membrane-less compartments that are observed under physiological and stress conditions, respectively. We observe that the trimeric PB protein DCP1A rapidly (within ∼10 s) phase-separates in mammalian cells during hyperosmotic stress and dissolves upon isosmotic rescue (over ∼100 s) with minimal impact on cell viability even after multiple cycles of osmotic perturbation. Strikingly, this rapid intracellular hyperosmotic phase separation (HOPS) correlates with the degree of cell volume compression, distinct from SG assembly, and is exhibited broadly by homo-multimeric (valency ≥ 2) proteins across several cell types. Notably, HOPS sequesters pre-mRNA cleavage factor components from actively transcribing genomic loci, providing a mechanism for hyperosmolarity-induced global impairment of transcription termination. Together, our data suggest that the multimeric proteome rapidly responds to changes in hydration and molecular crowding, revealing an unexpected mode of globally programmed phase separation and sequestration that adapts the cell to volume change.GRAPHICAL ABSTRACTIN BRIEFCells constantly experience osmotic variation. These external changes lead to changes in cell volume, and consequently the internal state of molecular crowding. Here, Jalihal and Pitchiaya et al. show that multimeric proteins respond rapidly to such cellular changes by undergoing rapid and reversible phase separation.HIGHLIGHTSDCP1A undergoes rapid and reversible hyperosmotic phase separation (HOPS)HOPS of DCP1A depends on its trimerization domainSelf-interacting multivalent proteins (valency ≥ 2) undergo HOPSHOPS of CPSF6 explains transcription termination defects during osmotic stress

scholarly journals Role of AQP2 in activation of calcium entry by hypotonicity: implications in cell volume regulation

2008 ◽  
Vol 294 (3) ◽  
pp. F582-F590 ◽  
Author(s):  
L. Galizia ◽  
M. P. Flamenco ◽  
V. Rivarola ◽  
C. Capurro ◽  
P. Ford
Keyword(s):  
Cell Membrane ◽  
Cell Volume ◽  
Volume Regulation ◽  
Collecting Duct ◽  
Regulatory Volume Decrease ◽  
Cell Volume Regulation ◽  
Calcium Entry ◽  
Cortical Collecting Duct ◽  
Extracellular Medium ◽  
Hypotonic Shock

We previously reported in a rat cortical collecting duct cell line (RCCD1) that the presence of aquaporin 2 (AQP2) in the cell membrane is critical for the rapid activation of regulatory volume decrease mechanisms (RVD) (Ford et al. Biol Cell 97: 687–697, 2005). The aim of our present work was to investigate the signaling pathway that links AQP2 to this rapid RVD activation. Since it has been previously described that hypotonic conditions induce intracellular calcium ([Ca2+]i) increases in different cell types, we tested the hypothesis that AQP2 could have a role in activation of calcium entry by hypotonicity and its implication in cell volume regulation. Using a fluorescent probe technique, we studied [Ca2+]i and cell volume changes in response to a hypotonic shock in WT-RCCD1 (not expressing aquaporins) and in AQP2-RCCD1 (transfected with AQP2) cells. We found that after a hypotonic shock only AQP2-RCCD1 cells exhibit a substantial increase in [Ca2+]i. This [Ca2+]i increase is strongly dependent on extracellular Ca2+ and is partially inhibited by thapsigargin (1 μM) indicating that the rise in [Ca2+]i reflects both influx from the extracellular medium and release from intracellular stores. Exposure of AQP2-RCCD1 cells to 100 μM gadolinium reduced the increase in [Ca2+]i suggesting the involvement of a mechanosensitive calcium channel. Furthermore, exposure of cells to all of the above described conditions impaired rapid RVD. We conclude that the expression of AQP2 in the cell membrane is critical to produce the increase in [Ca2+]i which is necessary to activate RVD in RCCD1 cells.

scholarly journals Swelling-activated Gd3+-sensitive Cation Current and Cell Volume Regulation in Rabbit Ventricular Myocytes

1997 ◽  
Vol 110 (3) ◽  
pp. 297-312 ◽  
Author(s):  
Henry F. Clemo ◽  
Clive M. Baumgarten
Keyword(s):  
Cell Volume ◽  
Volume Change ◽  
Volume Regulation ◽  
Ventricular Myocytes ◽  
Cell Volume Regulation ◽  
Hill Coefficient ◽  
Physiological Processes ◽  
Cation Current ◽  
Voltage Dependent ◽  
Rabbit Ventricular Myocytes

The role of swelling-activated currents in cell volume regulation is unclear. Currents elicited by swelling rabbit ventricular myocytes in solutions with 0.6–0.9× normal osmolarity were studied using amphotericin perforated patch clamp techniques, and cell volume was examined concurrently by digital video microscopy. Graded swelling caused graded activation of an inwardly rectifying, time-independent cation current (ICir,swell) that was reversibly blocked by Gd3+, but ICir,swell was not detected in isotonic or hypertonic media. This current was not related to IK1 because it was insensitive to Ba2+. The PK/PNa ratio for ICir,swell was 5.9 ± 0.3, implying that inward current is largely Na+ under physiological conditions. Increasing bath K+ increased gCir,swell but decreased rectification. Gd3+ block was fitted with a K0.5 of 1.7 ± 0.3 μM and Hill coefficient, n, of 1.7 ± 0.4. Exposure to Gd3+ also reduced hypotonic swelling by up to ∼30%, and block of current preceded the volume change by ∼1 min. Gd3+-induced cell shrinkage was proportional to ICir,swell when ICir,swell was varied by graded swelling or Gd3+ concentration and was voltage dependent, reflecting the voltage dependence of ICir,swell. Integrating the blocked ion flux and calculating the resulting change in osmolarity suggested that ICir,swell was sufficient to explain the majority of the volume change at –80 mV. In addition, swelling activated an outwardly rectifying Cl− current, ICl,swell. This current was absent after Cl− replacement, reversed at ECl, and was blocked by 1 mM 9-anthracene carboxylic acid. Block of ICl,swell provoked a 28% increase in swelling in hypotonic media. Thus, both cation and anion swelling-activated currents modulated the volume of ventricular myocytes. Besides its effects on cell volume, ICir,swell is expected to cause diastolic depolarization. Activation of ICir,swell also is likely to affect contraction and other physiological processes in myocytes.

scholarly journals Cell volume regulation in cancer cell migration driven by osmotic water flow

2019 ◽  
Vol 110 (8) ◽  
pp. 2337-2347 ◽  
Author(s):  
Kazuhiro Morishita ◽  
Kengo Watanabe ◽  
Hidenori Ichijo
Keyword(s):  
Cell Migration ◽  
Cell Volume ◽  
Water Flow ◽  
Cancer Cell ◽  
Volume Regulation ◽  
Cell Volume Regulation ◽  
Cancer Cell Migration ◽  
Osmotic Water ◽  
Osmotic Water Flow

Anisosmotic cell volume regulation: a comparative view

1989 ◽  
Vol 257 (2) ◽  
pp. C159-C173 ◽  
Author(s):  
M. E. Chamberlin ◽  
K. Strange
Keyword(s):  
Cell Volume ◽  
Intracellular Signaling ◽  
Volume Regulation ◽  
Cell Volume Regulation ◽  
Future Research ◽  
Organic Osmolytes ◽  
Organic Solutes ◽  
Transport Pathways ◽  
Perspective Drawing ◽  
Inorganic And Organic

A variety of organisms and cell types spanning the five taxonomic kingdoms are exposed, either naturally or through experimental means, to osmotic stresses. A common physiological response to these challenges is maintenance of cell volume through changes in the concentration of intracellular inorganic and organic solutes, collectively termed osmolytes. Research on the mechanisms by which the concentration of these solutes is regulated has proceeded along several experimental lines. Extensive studies on osmotically activated ion transport pathways have been carried out in vertebrate cells and tissues. Much of our knowledge on organic osmolytes has come from investigations on invertebrates, bacteria, and protists. The relative simplicity of bacterial genetics has provided a powerful and elegant tool to explore the modifications of gene expression during volume regulation. An implication of this diverse experimental approach is that phylogenetically divergent organisms employ uniquely adapted mechanisms of cell volume regulation. Given the probability that changes in extracellular osmolality were physiological stresses faced by the earliest organisms, it is more likely that cell volume regulation proceeds by highly conserved physiological processes. We review volume regulation from a comparative perspective, drawing examples from all five taxonomic kingdoms. Specifically, we discuss the role of inorganic and organic solutes in volume maintenance and the mechanisms by which the concentrations of these osmolytes are regulated. In addition, the processes that may transduce volume perturbations into regulatory responses, such as stretch activation of ion channels, intracellular signaling, and genomic regulation, are discussed. Throughout this review we emphasize areas we feel are important for future research.

scholarly journals 651 Organic osmolytes improve cell volume regulation of aged human keratinocytes

2018 ◽  
Vol 138 (5) ◽  
pp. S111
Author(s):  
A.R. Foster ◽  
C. El Chami ◽  
C.A. O'Neill ◽  
R.E.B. Watson
Keyword(s):  
Cell Volume ◽  
Volume Regulation ◽  
Cell Volume Regulation ◽  
Human Keratinocytes ◽  
Organic Osmolytes

Microfluidic Cell Volume Biosensor for High Throughput Drug Screening

2004 ◽  
Vol 845 ◽  
Author(s):  
Daniel A. Ateya ◽  
Frederick Sachs ◽  
Susan Z. Hua
Keyword(s):  
Cell Volume ◽  
Volume Change ◽  
Cell Volume Regulation ◽  
High Sensitivity ◽  
Rapid Screening ◽  
Osmotic Gradient ◽  
Physiological Processes ◽  
High Throughput Drug Screening ◽  
Microfluidic Chamber ◽  
Pharmaceutical Agents

ABSTRACTThe maintenance of cell volume is critical to health. Cell volume change reflects many biological and physiological processes. We have developed a lab-chip to measure cell volume change in real-time with high sensitivity and resolution, and applicable to both adherent and suspended cell populations. The volume change was detected by measuring the impedance of extra-cellular solution within a microfluidic chamber containing the cells. Using microfabrication to make precise chamber dimensions, volume change can be detected in response to an osmotic gradient <1mOsm. The sensor provides rapid screening of pharmaceutical agents affecting cell volume. We have screened for peptides that affect cell volume regulation and found one in spider venom that inhibits at ∼100pM.

Developmentally regulated cell cycle dependence of swelling-activated anion channel activity in the mouse embryo

Development ◽  
2001 ◽  
Vol 128 (18) ◽  
pp. 3427-3434 ◽  
Author(s):  
Marika Kolajova ◽  
Mary-Anne Hammer ◽  
Jennifer L. Collins ◽  
Jay M. Baltz
Keyword(s):  
Cell Cycle ◽  
Cell Volume ◽  
Cell Volume Regulation ◽  
Germinal Vesicle ◽  
Anion Channel ◽  
Mouse Embryos ◽  
Organic Osmolytes ◽  
Developmentally Regulated ◽  
Cell Stage ◽  
Cycle Dependent

Anion channels activated by increased cell volume are a nearly ubiquitous mechanism of cell volume regulation, including in early preimplantation mouse embryos. Here, we show that the swelling-activated anion current (ICl,swell) in early mouse embryos is cell-cycle dependent, and also that this dependence is developmentally regulated. ICl,swell is present both in first meiotic prophase (germinal vesicle stage) mouse oocytes and in unfertilized mature oocytes in second meiotic metaphase, and it persists after fertilization though the 1-cell and 2-cell stages. ICl,swell was found to remain unchanged during metaphase at the end of the 1-cell stage. However, ICl,swell decreased during prophase and became nearly undetectable upon entry into metaphase at the end of the 2-cell stage. Entry into prophase/metaphase was required for the decrease in ICl,swell at the end of the 2-cell stage, since it persisted indefinitely in 2-cell embryos arrested in late G2. There is considerable evidence that the channel underlying ICl,swell is not only permeable to inorganic anions, but to organic osmolytes as well. We found a similar pattern of cell cycle and developmental dependence in the 1-cell and 2-cell stages for the swelling-induced increase in permeability to the organic osmolyte glycine. Thus, entry into metaphase deactivates ICl,swell in embryos, but only after developmental progression through the 2-cell stage.

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