ENDOSOMAL MEMBRANE TENSION CONTROLS ESCRT-III-DEPENDENT INTRA-LUMENAL VESICLE FORMATION
Posted on: 26 February 2019 , updated on: 27 February 2019
Preprint posted on 21 February 2019
Article now published in Nature Cell Biology at http://dx.doi.org/10.1038/s41556-020-0546-4
Feeling tense? Hop aboard! Endosomal ESCRT-III recruitment and ILV formation is regulated by endosomal membrane tension
Selected by Nicola Stevenson
Categories: biochemistry, biophysics, cell biology
Background
During endosomal protein sorting, five large multisubunit protein assemblies, collectively known as the ESCRT machinery (Endosomal Sorting Complexes Required for Transport), assemble in a sequential manner on the endosome surface to generate intraluminal vesicles – vesicles that bud into the lumen of the endosome to generate multivesicular bodies. The fourth of these assemblies, ESCRT-III, is largely cytoplasmic and only transiently assembles on endosomes during sorting. Once recruited here it deubiquitinates and sequesters cargo in the vesicle and reorganises the membrane for budding and scission (1). Previous reports have shown that ESCRT-III depends on other members of the ESCRT machinery, such as VPS25 of ESCRT-II (2), to localise to membranes. However, in this new study, Mercier et al report that ESCRT-III is rapidly recruited to the endosome following a decrease in membrane tension, such as occurs during stimulated recycling of the EGF receptor. This provides a fascinating new regulatory link between the physical properties of organelles and the recruitment of large protein machines. Such a link may allow fluctuations in the extracellular environment to propagate changes in cell behaviour independent of (or augmenting) specific signalling molecules.
Key findings
In this study the authors use two methods to induce changes in endosomal membrane tension inside the cell; 1) hypertonic shock with sucrose or NaCl and 2) transient permeabilization of the endosome membrane using the small peptide LLOMe. Changes in membrane tension were confirmed with the fluorescent lipid tension reporter, Lyso Flipper. In both cases, a reduction in membrane tension induced the transient relocation of the ESCRT-III component CHMP4B from a diffuse cytosolic localisation to EEA1 positive endosomes. This endosomal recruitment is selective for ESCRT-III, since ESCRT-0 and ESCRT-1 were not recruited to membranes upon hypertonic shock and STAM and TSG101 only partially so on LLOMe treatment. Recruitment is, however, in part dependent on the ESCRT-III nucleator ALIX and recruited assemblies are functional.
These results were confirmed using a third method in which recombinant CHMP4B was incubated with giant unilamellar vesicles. In isotonic conditions CHMP4B recruited slowly to these membranes, however switching to hypertonic solution increased CHMP4B recruitment three-fold. Changing membrane tension by pulling on the membranes with optical tweezers also demonstrated a negative correlation between increasing membrane tension and CHMP4B recruitment. Electron microscopy of membranes coated with CHMP4B were tubular and deformed indicating CHMP4B recruitment induced membrane remodelling.
Finally, to show membrane tension regulated recruitment of ESCRT-III is physiologically relevant, the authors treated cells with epidermal growth factor (EGF) to stimulate recycling of its receptor through endosomes. Treatment increased ESCRT dependent ILV formation concurrent with a reduction in endosome membrane tension as detected with Lyso Flipper. Such a reduction in membrane tension is likely brought about by the increase in membrane surface area as endosomal vesicles carrying the EGF receptor fuse with mature endosomes.
In conclusion, CHMP4B polymerises on endosomal membranes when membrane tension is lowered.
Perspective
With the advent of atomic force microscopy and optical tweezers, the study of membrane tension and cell behaviour has become a more popular and attainable pursuit in recent years. Understandably, research in this area has been predominantly, but not exclusively, focused on the plasma membrane due to its accessibility and amenability to such techniques. However, the recent development of fluorescent membrane tension sensors by some of the authors of this study (3) has provided the opportunity to expand these investigations to the study of internal membranes. These should help to elucidate the full extent to which mechanosensation is important to cellular function. I chose to highlight this paper as it is a good example of the potential of this avenue of study. Current models of membrane trafficking events generally focus on chemical interactions between proteins, lipids and small molecules but this study demonstrates that this is only part of the picture. Clearly we need to look beyond biochemistry to biophysics to really understand this process.
Future questions
- Why is ESCRT-III but not upstream components of ESCRT recruited in this way? Changes in membrane tension are likely to occur very rapidly following stimulated endocytosis and so one may imagine this would be relevant to the initiation of ESCRT-mediated sorting rather than later steps. Is ESCRT-III playing another role on the endosomes i.e. reducing membrane surface in a compensatory manner?
- What are the key features of the CHMP4B or its recruitment factors that enable membrane tension sensing?
- Is membrane tension a global mechanism for sensing and responding to changes in membrane flux between organelles or is this specific to ILV formation. Some external stimuli can increase anterograde secretion, for example synaptic transmission can stimulate the ER export of de novo synaptic receptors to the cell surface. Does this similarly result in changes in membrane tension and recruitment of proteins for membrane remodelling?
References
- Raiborg, C., Stenmark, H. The ESCRT machinery in endosomal sorting of ubiquitylated membrane proteins. Nature 458, 445-452 (2009)
- Teo, H., Perisic, O., Gonzalez, B. & Williams, R. L. ESCRT-II, an endosome-associated complex required for protein sorting: crystal structure and interactions with ESCRT-III and membranes. Cell7, 559–569 (2004)
- Goujon, A., Colom, A., Straková, K., Mercier, V., Mahecic, D., Manley, S., Sakai, N., Roux, A., & Matile, S. Mechanosensitive Fluorescent Probes to Image Membrane Tension in Mitochondria, Endoplasmic Reticulum, and Lysosomes. Am. Chem. Soc (2019)
doi: https://doi.org/10.1242/prelights.8971
Read preprint
(1 votes) Sign up to customise the site to your preferences and to receive alerts
Register hereAlso in the biochemistry category:
Triglyceride metabolism controls inflammation and APOE4-associated disease states in microglia
Gustavo Stelzer, Marcus Oliveira
Impaired 26S proteasome causes learning and memory deficiency and induces neuroinflammation mediated by NF-κB in mice
Gustavo Stelzer, Marcus Oliveira
Notch3 is a genetic modifier of NODAL signalling for patterning asymmetry during mouse heart looping
Bhaval Parmar
Also in the biophysics category:
Restoring mechanophenotype reverts malignant properties of ECM-enriched vocal fold cancer
Teodora Piskova
Motor Clustering Enhances Kinesin-driven Vesicle Transport
Sharvari Pitke
Global coordination of protrusive forces in migrating immune cells
yohalie kalukula
Also in the cell biology category:
Restoring mechanophenotype reverts malignant properties of ECM-enriched vocal fold cancer
Teodora Piskova
Germplasm stability in zebrafish requires maternal Tdrd6a and Tdrd6c
Justin Gutkowski
Leukocytes use endothelial membrane tunnels to extravasate the vasculature
Felipe Del Valle Batalla
preLists in the biochemistry category:
BSCB-Biochemical Society 2024 Cell Migration meeting
This preList features preprints that were discussed and presented during the BSCB-Biochemical Society 2024 Cell Migration meeting in Birmingham, UK in April 2024. Kindly put together by Sara Morais da Silva, Reviews Editor at Journal of Cell Science.
| List by | Reinier Prosee |
Peer Review in Biomedical Sciences
Communication of scientific knowledge has changed dramatically in recent decades and the public perception of scientific discoveries depends on the peer review process of articles published in scientific journals. Preprints are key vehicles for the dissemination of scientific discoveries, but they are still not properly recognized by the scientific community since peer review is very limited. On the other hand, peer review is very heterogeneous and a fundamental aspect to improve it is to train young scientists on how to think critically and how to evaluate scientific knowledge in a professional way. Thus, this course aims to: i) train students on how to perform peer review of scientific manuscripts in a professional manner; ii) develop students' critical thinking; iii) contribute to the appreciation of preprints as important vehicles for the dissemination of scientific knowledge without restrictions; iv) contribute to the development of students' curricula, as their opinions will be published and indexed on the preLights platform. The evaluations will be based on qualitative analyses of the oral presentations of preprints in the field of biomedical sciences deposited in the bioRxiv server, of the critical reports written by the students, as well as of the participation of the students during the preprints discussions.
| List by | Marcus Oliveira et al. |
CellBio 2022 – An ASCB/EMBO Meeting
This preLists features preprints that were discussed and presented during the CellBio 2022 meeting in Washington, DC in December 2022.
| List by | Nadja Hümpfer et al. |
20th “Genetics Workshops in Hungary”, Szeged (25th, September)
In this annual conference, Hungarian geneticists, biochemists and biotechnologists presented their works. Link: http://group.szbk.u-szeged.hu/minikonf/archive/prg2021.pdf
| List by | Nándor Lipták |
Fibroblasts
The advances in fibroblast biology preList explores the recent discoveries and preprints of the fibroblast world. Get ready to immerse yourself with this list created for fibroblasts aficionados and lovers, and beyond. Here, my goal is to include preprints of fibroblast biology, heterogeneity, fate, extracellular matrix, behavior, topography, single-cell atlases, spatial transcriptomics, and their matrix!
| List by | Osvaldo Contreras |
ASCB EMBO Annual Meeting 2019
A collection of preprints presented at the 2019 ASCB EMBO Meeting in Washington, DC (December 7-11)
| List by | Madhuja Samaddar et al. |
EMBL Seeing is Believing – Imaging the Molecular Processes of Life
Preprints discussed at the 2019 edition of Seeing is Believing, at EMBL Heidelberg from the 9th-12th October 2019
| List by | Dey Lab |
Cellular metabolism
A curated list of preprints related to cellular metabolism at Biorxiv by Pablo Ranea Robles from the Prelights community. Special interest on lipid metabolism, peroxisomes and mitochondria.
| List by | Pablo Ranea Robles |
MitoList
This list of preprints is focused on work expanding our knowledge on mitochondria in any organism, tissue or cell type, from the normal biology to the pathology.
| List by | Sandra Franco Iborra |
Also in the biophysics category:
preLights peer support – preprints of interest
This is a preprint repository to organise the preprints and preLights covered through the 'preLights peer support' initiative.
| List by | preLights peer support |
66th Biophysical Society Annual Meeting, 2022
Preprints presented at the 66th BPS Annual Meeting, Feb 19 - 23, 2022 (The below list is not exhaustive and the preprints are listed in no particular order.)
| List by | Soni Mohapatra |
EMBL Synthetic Morphogenesis: From Gene Circuits to Tissue Architecture (2021)
A list of preprints mentioned at the #EESmorphoG virtual meeting in 2021.
| List by | Alex Eve |
Biophysical Society Meeting 2020
Some preprints presented at the Biophysical Society Meeting 2020 in San Diego, USA.
| List by | Tessa Sinnige |
ASCB EMBO Annual Meeting 2019
A collection of preprints presented at the 2019 ASCB EMBO Meeting in Washington, DC (December 7-11)
| List by | Madhuja Samaddar et al. |
EMBL Seeing is Believing – Imaging the Molecular Processes of Life
Preprints discussed at the 2019 edition of Seeing is Believing, at EMBL Heidelberg from the 9th-12th October 2019
| List by | Dey Lab |
Biomolecular NMR
Preprints related to the application and development of biomolecular NMR spectroscopy
| List by | Reid Alderson |
Biophysical Society Annual Meeting 2019
Few of the preprints that were discussed in the recent BPS annual meeting at Baltimore, USA
| List by | Joseph Jose Thottacherry |
Also in the cell biology category:
November in preprints – the CellBio edition
This is the first community-driven preList! A group of preLighters, with expertise in different areas of cell biology, have worked together to create this preprint reading lists for researchers with an interest in cell biology. Categories include: 1) cancer cell biology 2) cell cycle and division 3) cell migration and cytoskeleton 4) cell organelles and organisation 5) cell signalling and mechanosensing 6) genetics/gene expression
| List by | Felipe Del Valle Batalla et al. |
BSCB-Biochemical Society 2024 Cell Migration meeting
This preList features preprints that were discussed and presented during the BSCB-Biochemical Society 2024 Cell Migration meeting in Birmingham, UK in April 2024. Kindly put together by Sara Morais da Silva, Reviews Editor at Journal of Cell Science.
| List by | Reinier Prosee |
‘In preprints’ from Development 2022-2023
A list of the preprints featured in Development's 'In preprints' articles between 2022-2023
| List by | Alex Eve, Katherine Brown |
preLights peer support – preprints of interest
This is a preprint repository to organise the preprints and preLights covered through the 'preLights peer support' initiative.
| List by | preLights peer support |
The Society for Developmental Biology 82nd Annual Meeting
This preList is made up of the preprints discussed during the Society for Developmental Biology 82nd Annual Meeting that took place in Chicago in July 2023.
| List by | Joyce Yu, Katherine Brown |
CSHL 87th Symposium: Stem Cells
Preprints mentioned by speakers at the #CSHLsymp23
| List by | Alex Eve |
Journal of Cell Science meeting ‘Imaging Cell Dynamics’
This preList highlights the preprints discussed at the JCS meeting 'Imaging Cell Dynamics'. The meeting was held from 14 - 17 May 2023 in Lisbon, Portugal and was organised by Erika Holzbaur, Jennifer Lippincott-Schwartz, Rob Parton and Michael Way.
| List by | Helen Zenner |
9th International Symposium on the Biology of Vertebrate Sex Determination
This preList contains preprints discussed during the 9th International Symposium on the Biology of Vertebrate Sex Determination. This conference was held in Kona, Hawaii from April 17th to 21st 2023.
| List by | Martin Estermann |
Alumni picks – preLights 5th Birthday
This preList contains preprints that were picked and highlighted by preLights Alumni - an initiative that was set up to mark preLights 5th birthday. More entries will follow throughout February and March 2023.
| List by | Sergio Menchero et al. |
CellBio 2022 – An ASCB/EMBO Meeting
This preLists features preprints that were discussed and presented during the CellBio 2022 meeting in Washington, DC in December 2022.
| List by | Nadja Hümpfer et al. |
Fibroblasts
The advances in fibroblast biology preList explores the recent discoveries and preprints of the fibroblast world. Get ready to immerse yourself with this list created for fibroblasts aficionados and lovers, and beyond. Here, my goal is to include preprints of fibroblast biology, heterogeneity, fate, extracellular matrix, behavior, topography, single-cell atlases, spatial transcriptomics, and their matrix!
| List by | Osvaldo Contreras |
EMBL Synthetic Morphogenesis: From Gene Circuits to Tissue Architecture (2021)
A list of preprints mentioned at the #EESmorphoG virtual meeting in 2021.
| List by | Alex Eve |
FENS 2020
A collection of preprints presented during the virtual meeting of the Federation of European Neuroscience Societies (FENS) in 2020
| List by | Ana Dorrego-Rivas |
Planar Cell Polarity – PCP
This preList contains preprints about the latest findings on Planar Cell Polarity (PCP) in various model organisms at the molecular, cellular and tissue levels.
| List by | Ana Dorrego-Rivas |
BioMalPar XVI: Biology and Pathology of the Malaria Parasite
[under construction] Preprints presented at the (fully virtual) EMBL BioMalPar XVI, 17-18 May 2020 #emblmalaria
| List by | Dey Lab, Samantha Seah |
1
Cell Polarity
Recent research from the field of cell polarity is summarized in this list of preprints. It comprises of studies focusing on various forms of cell polarity ranging from epithelial polarity, planar cell polarity to front-to-rear polarity.
| List by | Yamini Ravichandran |
TAGC 2020
Preprints recently presented at the virtual Allied Genetics Conference, April 22-26, 2020. #TAGC20
| List by | Maiko Kitaoka et al. |
3D Gastruloids
A curated list of preprints related to Gastruloids (in vitro models of early development obtained by 3D aggregation of embryonic cells). Updated until July 2021.
| List by | Paul Gerald L. Sanchez and Stefano Vianello |
ECFG15 – Fungal biology
Preprints presented at 15th European Conference on Fungal Genetics 17-20 February 2020 Rome
| List by | Hiral Shah |
ASCB EMBO Annual Meeting 2019
A collection of preprints presented at the 2019 ASCB EMBO Meeting in Washington, DC (December 7-11)
| List by | Madhuja Samaddar et al. |
EMBL Seeing is Believing – Imaging the Molecular Processes of Life
Preprints discussed at the 2019 edition of Seeing is Believing, at EMBL Heidelberg from the 9th-12th October 2019
| List by | Dey Lab |
Autophagy
Preprints on autophagy and lysosomal degradation and its role in neurodegeneration and disease. Includes molecular mechanisms, upstream signalling and regulation as well as studies on pharmaceutical interventions to upregulate the process.
| List by | Sandra Malmgren Hill |
Lung Disease and Regeneration
This preprint list compiles highlights from the field of lung biology.
| List by | Rob Hynds |
Cellular metabolism
A curated list of preprints related to cellular metabolism at Biorxiv by Pablo Ranea Robles from the Prelights community. Special interest on lipid metabolism, peroxisomes and mitochondria.
| List by | Pablo Ranea Robles |
BSCB/BSDB Annual Meeting 2019
Preprints presented at the BSCB/BSDB Annual Meeting 2019
| List by | Dey Lab |
MitoList
This list of preprints is focused on work expanding our knowledge on mitochondria in any organism, tissue or cell type, from the normal biology to the pathology.
| List by | Sandra Franco Iborra |
ASCB/EMBO Annual Meeting 2018
This list relates to preprints that were discussed at the recent ASCB conference.
| List by | Dey Lab, Amanda Haage |