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Developmental Biology - Cell Structure
Some Tension is Good in Life
The tension on each cell of your body governs your life...
As every animal has its characteristic size and shape, each type of cell in our body has a size and shape. Neurons (nerve cells) are very different from muscle cells that are dramatically different from the cells in bone. All these cells look different, perform unique functions, share with each other and multiply, while maintaining their individual size and function.
The plasma membrane of a cell defines its boundary and thus its size. However, the cell membrane is not a static wall — it is in constant flux. Every moment it "talks" to its surroundings.
Cells take up nutrients and other material from their surroundings in a process called endocytosis, bending the cellular membrane inward to form a vesicle to contain any foreign material. The origin of the word explains its functional meaning: Endon - within, kytos - cell, or uptake of material from its environment by invagination of its plasma membrane.
However, in order to envelope foreign materials entering the cell, a bit of the cell's plasma membrane is taken too. If not careful, the cell could shrink in size due to this loss of membrane. Exocytosis, on the other hand, adds to the cell membrane surface by adding vesicles. So, a cell will shrink or enlarge depending on the processes called for in maintaining a balance within its community of cells.
A cell must make multiple entry and exit doors every moment of every day in order to absorb, or remove, material inside its membrane.
This research is published in Nature Communications.
Not unlike the 'Jedi Knights'of Star Wars mythology, cells maintain their interior balance by using the force — the force created by membrane tension. A myriad of endocytic pathways operate in parallel on a micron scale quick to sense and respond to changes in force on the cell membrane. This micron pathway is called the CLIC/GEEC pathway. Increasing membrane tension decreases the endocytic pathway while decreasing membrane tension increases endocytosis. As the CLIC/GEEC pathway senses and responds to changes in plasma membrane force, it mediates many endocytic mechanisms.
Every time a door and piece of wall is removed in endocytosis — membrane tension increases. The cell senses and responds to this change in tension by adding membrane, thus homeostasis in the cell membrane is maintained.
How does the cell convert physical information into a bio-chemical response? Reseachers identified that the molecule vinculin remains closed under low force and opens up under high force. Vinculin in an open state inhibits an upstream regulator of the CLIC/GEEC pathway. If the membrane force increases, the CLIC/GEEC pathway shuts down and the membrane relaxes. When tension lowers, endocytosis increases and extra membrane is absorbed.
The cell uses vinculin to both open and close in response to cell membrane tension. As a cell constantly measures and responds to tension through this pathway, it is able to maintain membrane homeostasis. Without which a cell — and life — cannot exist.
CLIC/GEEC endocytosis is also hijacked by viruses to enter cells; and used by cancer cells to spread to different organs. The study shows the importance of understanding all cellular processes for fighting cancers effectively.
Abstract
Plasma membrane tension regulates many key cellular processes. It is modulated by, and can modulate, membrane trafficking. However, the cellular pathway(s) involved in this interplay is poorly understood. Here we find that, among a number of endocytic processes operating simultaneously at the cell surface, a dynamin independent pathway, the CLIC/GEEC (CG) pathway, is rapidly and specifically upregulated upon a sudden reduction of tension. Moreover, inhibition (activation) of the CG pathway results in lower (higher) membrane tension. However, alteration in membrane tension does not directly modulate CG endocytosis. This requires vinculin, a mechano-transducer recruited to focal adhesion in adherent cells. Vinculin acts by controlling the levels of a key regulator of the CG pathway, GBF1, at the plasma membrane. Thus, the CG pathway directly regulates membrane tension and is in turn controlled via a mechano-chemical feedback inhibition, potentially leading to homeostatic regulation of membrane tension in adherent cells.
Authors
Joseph Jose Thottacherry, Anita Joanna Kosmalska, Amit Kumar, Amit Singh Vishen, Alberto Elosegui-Artola, Susav Pradhan, Sumit Sharma, Parvinder P. Singh, Marta C. Guadamillas, Natasha Chaudhary, Ram Vishwakarma, Xavier Trepat, Miguel A. del Pozo, Robert G. Parton, Madan Rao, Pramod Pullarkat, Pere Roca-Cusachs and Satyajit Mayor.
Acknowledgements
The authors wish to thank Pietro De Camilli (Yale University, USA) for conditional Dynamin triple knockout cell line, Daniel Rösel (Charles University, Prague) for vinculin-null cell line, Darius V. Köster for the caveolin-null cell line, David J. Stephens (University of Bristol, UK) for an initial gift of LG186, Philippe Benaroch (Institut Curie, Paris) for AP2 shRNA, Clare M. Waterman (NIH, USA) for vinculin constructs, Feroz M.H. Musthafa (CCAMP, Bangalore) and G.V. Soni (RRI, Bangalore) for help with preparation of PDMS membrane. We would like to thank Manoj Mathew and central imaging and flow cytometry facility (CIFF, NCBS) for help with imaging, Dev Kumar (Mech. Workshop) for making components for stretch–relax apparatus and imaging, Dr. Anusuya Banerjee for help with illustrations, K. Joseph Mathew for final cartoon and thank members of P.P., X.T. and P.R-C. laboratories for hosting and helping J.J.T. with day-to-day experiments. X.T. acknowledges support from the Spanish Ministry of Economy and Competitiveness (BFU2015-65074-P), the Generalitat de Catalunya (2014-SGR-927) and the European Research Council (ERC-2013-CoG-616480). This work was supported by the Spanish Ministry of Economy and Competitiveness (BFU2016-79916-P to P.R.-C.), the European Commission (H2020-FETPROACT-01-2016-731957 to X.T. and P.R.-C.) and Obra Social 'La Caixa'. A.E.-A. acknowledges support by Juan de la Cierva Fellowship from Spanish Ministry of Economy and Competitiveness (IJCI-2014-19156). This study was also supported by grants SAF2014-51876-R from Spanish Ministry of Economy and Competitiveness (MINECO) and co-funded by FEDER funds to M.A.d.P., and 674/C/2013 from Fundació La Marató de TV3 to P.R.-C. and M.A.d.P. R.G.P. was supported by the National Health and Medical Research Council (NHMRC) of Australia (program grant, APP1037320 and Senior Principal Research Fellowship, 569452), and the Australian Research Council Centre of Excellence (CE140100036). We acknowledge the Australian Microscopy and Microanalysis Research Facility at the Center for Microscopy and Microanalysis at The University of Queensland. J.J.T. acknowledges pre-doctoral fellowship from Council for Scientific and Industrial Research (CSIR), Government of India. S.M. would like to acknowledge J.C. Bose Fellowship from DST, Government of India, and Wellcome Trust-DBT Margdarshi fellowship (IA/M/15/1/502018).
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Jan 11, 2019 Fetal Timeline Maternal Timeline News News Archive
 The cell wall responds to membrane strain by invagination at points (puncta) of the membrane in contact with a foreign substance, pulling the wall into vacuoles (RED) that surround the substance — ENDOCYTOSIS. Also, by expelling contents of a cell vacuole to the exterior of the cell via fusion of the vacuole membrane to the cell membrane — EXOCYTOSIS (GREEN). These two parallel responses on a cell membrane balance its tension thus maintaining cell size. Image: Joseph Jose Thottacherry.
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