Endomembrane Tension and Trafficking

Abstract

Eukaryotic cells employ diverse uptake mechanisms depending on their specialized functions. While such mechanisms vary widely in their defining criteria: scale, molecular machinery utilized, cargo selection, and cargo destination, to name a few, they all result in the internalization of extracellular solutes and fluid into membrane-bound endosomes. Upon scission from the plasma membrane, this compartment is immediately subjected to extensive remodeling which involves tubulation and vesiculation/budding of the limiting endomembrane. This is followed by a maturation process involving concomitant retrograde transport by microtubule-based motors and graded fusion with late endosomes and lysosomes, organelles that support the degradation of the internalized content. Here we review an important determinant for sorting and trafficking in early endosomes and in lysosomes; the control of tension on the endomembrane. Remodeling of endomembranes is opposed by high tension (caused by high hydrostatic pressure) and supported by the relief of tension. We describe how the timely and coordinated efflux of major solutes along the endocytic pathway affords the cell control over such tension. The channels and transporters that expel the smallest components of the ingested medium from the early endocytic fluid are described in detail as these systems are thought to enable endomembrane deformation by curvature-sensing/generating coat proteins. We also review similar considerations for the lysosome where resident hydrolases liberate building blocks from luminal macromolecules and transporters flux these organic solutes to orchestrate trafficking events. How the cell directs organellar trafficking based on the luminal contents of organelles of the endocytic pathway is not well-understood, however, we propose that the control over membrane tension by solute transport constitutes one means for this to ensue.

Photocleavable Fluorescent Membrane Tension Probes: Fast Release with Spatiotemporal Control in Inner Leaflets of Plasma Membrane, Nuclear Envelope, and Secretory Pathway

“…The imaging of order and particularly physical tension in biomembranes with fluorescent probes is a topic of current concern [1–3] . Beginning with the original 1 , “Flipper” probes have been introduced to tackle this challenge with a planarizable push‐pull mechanophore that responds to membrane compression with a red shift in excitation and an increase in fluorescence lifetime (Figure 1, Figure 2 A).…”

Active targeting via ligand-anchored pH-responsive strontium nanoparticles for efficient nucleic acid delivery into breast cancer cells

“…The use of reporter plasmids including green fluorescent protein (pGFP) and firefly luciferase (pGL3) allows for a distinctly sensitive and powerful approach in determining the effectiveness of the potential carrier to facilitate the gene transfer and expression in the nucleus, as determined by the presence of fluorescent and luminescent signals (Pajarinen et al 2015). The intracellular carrier potentiality is determined by nucleic acid escape from the particle complexes before the content is subjected to the lysosomal degradation or exocytosis via a transcellular pump located in the cellular membrane (Saric and Freeman 2021).…”

From Pinocytosis to Methuosis—Fluid Consumption as a Risk Factor for Cell Death

“…Also, proteins of the ESCRT complexes take advantage of the slack membrane to induce inwardly budding intraluminal vesicles (ILVs) and further on MVBs. Thus, the vesicular shrinkage creates organelles with high surface-to-volume ratios, relieves the hydrostatic tension of their membranes, and is hence critical for their resolution (for review, see Freeman and Grinstein, 2018 ; Chen et al, 2020b ; Saric and Freeman, 2020 , 2021 ; Chadwick et al, 2021a , b ).…”

“…Recent studies indicate that volume regulation in cells and cell organelles is governed by the same biophysical principles and by the overlapping use of ion channels and transporters in distinct cellular compartments ( Saric and Freeman, 2020 , 2021 ; Chadwick et al, 2021a , b ). That is, it starts with the asymmetric distribution of ions and materializes in the well-orchestrated uptake and processing of engulfed material in specialized vesicles ( Chadwick et al, 2021a ).…”