Menu

Close

Clathrin plaques form mechanotransducing platforms

Agathe Franck, Jeanne Laine, Gilles Moulay, Michael Trichet, Christel Gentil, Anais Fongy, Anne Bigot, Sofia Benkhelifa-Ziyyat, Emmanuelle Lacene, Mai Thao Bui, Guy Brochier, Pascale Guicheney, Vincent Mouly, Norma Beatriz Romero, Catherine Coirault, Marc Bitoun, Stephane Vassilopoulos

Preprint posted on May 14, 2018 https://www.biorxiv.org/content/early/2018/05/14/321885?%3Fcollection=

Clathrin plaques are the new focal adhesions: Adhesive clathrin plaque association with the cytoskeleton provides a novel platform for mechanosensing, including the regulation of YAP/TAZ signaling.

Selected by Amanda Haage

Categories: biophysics, cell biology

Why This Is Cool – The authors provide evidence that two relatively new discoveries in cell biology, mechanotransduction via YAP/TAZ signaling and large clathrin plaque structures on the plasma membrane, work together to produce a novel platform for sensing mechanical input, connecting and regulating the cytoskeleton, and integrating various signaling pathways. These are the roles that have previously been established for focal adhesions. It makes sense that cells could complete these essential tasks in a variety of ways using other large membrane-associated protein complexes. The authors provide exhaustive evidence for the mechanisms and relevance of this new system. First, they demonstrate using beautiful images of immunogold labeling with metal-replica EM (Fig1) the precise organization of the clathrin plaques surrounded by branched actin and desmin intermediate filaments on primary mouse myotubes. Next they show that these structures respond to mechanical stimuli by subjecting the myotubes to cyclic stretching. Upon stretching the plaques decrease in size supposedly due to an increase in endocytosis and the YAP/TAZ mechanotransducers canonically accumulate in the nucleus with a concurrent increase in their target genes’ expression levels. Interestingly, myotubes without clathrin plaques had high levels of YAP/TAZ nuclear staining without stretching with no obvious response to stretch. The authors go on to demonstrate this is because the clathrin plaques act as sticky nets that sequester YAP/TAZ until the cell receives a mechanical input. They propose that YAP/TAZ gets stuck at the actin network surrounding clathrin plaques largely through an interaction between TAZ and Dynamin 2. Myotubes without Dynamin 2 lose their actin organization, and their ability to translocate YAP/TAZ in response to stretch. Now that they have established a mechanism for how clathrin plaques can act as mechanosensors, the authors go on to show the relevance of this mechanism in vivo. A type of centronuclear myopathy is caused by mutations in Dynamin 2. By using a knock-in mouse model for the most common human mutation linked to this disease, they demonstrate similar phenotypes to the Dynamin 2 knockout myotubes. These mice were found to have disorganized clathrin plaques, TAZ, and desmin in their muscles. In addition, primary culture of their mytotubes revealed a decrease in TAZ nuclear localization without mechanical input. To really drive the point home, the authors also repeat these findings in immortalized myotubes from a centronuclear myopathy human patient.

Fig. 1 (adapted from preprint). Clathrin-coated plaques are required for intermediate filament organization. (A) Immunofluorescent staining of α-actinin 2 (green), CHC (magenta), and actin (red) in extensively differentiated mouse primary myotubes. Bars are 10 µm and 2 µm for insets. (B) Survey view of unroofed primary mouse myotube differentiated for 15 days. (C) (D) Higher magnification views corresponding to the boxed regions in b.

 

Why I Selected It – The idea that cells can sense and respond to the physical properties of their microenvironment has always fascinated me. It’s a newer concept that has burst into a huge field of cell biology. We are now getting beyond the initial discoveries of this phenomenon and learning just how much it permeates every part of cell biology. Mechanotransduction is not just a field for cell migration or extracellular matrix people, but is a field for everyone.

Open Questions –

  1. Has YAP/TAZ translocation via endocytosis been directly observed? Is it something that could be observed via live imaging?
  2. Do the clathrin plaques ever recover in size and YAP/TAZ content after extended periods of relaxation?
  3. Could the Dynamin 2 – TAZ interaction be a realistic drug target for centronuclear myopathy?

Related References –

  1. What is YAP/TAZ?
    1. Dupont S. Role of YAP/TAZ in cell-matrix adhesion-mediates signaling and mechanotransduction. Exp Cell Res. (2016) 10;343(1):42-53/
  2. What are clathrin plaques?
    1. Lampe M., Vassilopoulos S., Merrifield C. Clathrin coated pits, plaques and adhesion. J Struct Biol. (2016) 196(1):48-56.
  3. Mutations in Dynamin 2 cause centronuclear myopathy
    1. Bitoun M., Maugenre S., Jeannet PY., Lacene E., Ferrer X., Laforet P., Martin JJ., Laporte J., Lochmuller H., Beggs AH., Fardeau M., Eymard B., Romero NB., Guicheney P. Mutations in dynamin 2 cause dominant centronuclear myopathy. Nat Genet. (2005) 37(11):1207-9.

 

Posted on: 6th June 2018

Read preprint (No Ratings Yet)




  • Have your say

    Your email address will not be published. Required fields are marked *

    Sign up to customise the site to your preferences and to receive alerts

    Register here

    Also in the biophysics category:

    Excitable RhoA dynamics drive pulsed contractions in the early C. elegans embryo.

    Jonathan B Michaux, Francois B Robin, William M McFadden, et al.



    Selected by Sundar Naganathan

    Dynamics and interactions of ADP/ATP transporter AAC3 in DPC detergent are not functionally relevant

    Vilius Kurauskas, Audrey Hessel, François Dehez, et al.

    AND

    Major concerns with the integrity of the mitochondrial ADP/ATP carrier in dodecyl-phosphocholine used for solution NMR studies

    Martin S. King, Paul G. Crichton, Jonathan J. Ruprecht, et al.



    Selected by Reid Alderson

    1

    Mechanosensitive binding of p120-Catenin at cell junctions regulates E-Cadherin turnover and epithelial viscoelasticity

    K. Venkatesan Iyer, Romina Piscitello-Gómez, Frank Jülicher, et al.



    Selected by Ivana Viktorinová

    Kinetic sculpting of the seven stripes of the Drosophila even-skipped gene

    Augusto Berrocal, Nicholas C Lammers, Hernan G Garcia, et al.



    Selected by Erik Clark

    Structural Basis of Tubulin Recruitment and Assembly by Tumor Overexpressed Gene (TOG) domain array Microtubule Polymerases

    Stanley Nithiananatham, Brian Cook, Fred Chang, et al.

    AND

    Roles for tubulin recruitment and self-organization by TOG domain arrays in Microtubule plus-end tracking and polymerase

    Brian Cook, Fred Chang, Ignacio Flor-Parra, et al.



    Selected by Ben Craske, Thibault Legal and Toni McHugh

    Molecular dynamics simulations disclose early stages of the photo-activation of cryptochrome 4

    Daniel R. Kattnig, Claus Nielsen, Ilia A. Solov'yov



    Selected by Miriam Liedvogel

    1

    Cellular Crowding Influences Extrusion and Proliferation to Facilitate Epithelial Tissue Repair

    Jovany Jeomar Franco, Youmna Maryline Atieh, Chase Dallas Bryan, et al.



    Selected by Helen Weavers

    Live-cell imaging of marked chromosome regions reveals dynamics of mitotic chromosome resolution and compaction

    John K Eykelenboom, Marek Gierlinski, Zuojun Yue, et al.

    AND

    Quantitative imaging of chromatin decompaction in living cells

    Elisa Dultz, Roberta Mancini, Guido Polles, et al.



    Selected by Carmen Adriaens, Gautam Dey

    Tissue flow induces cell shape changes during organogenesis

    Gonca Erdemci-Tandogan, Madeline J.Clark, Jeffrey D. Amack, et al.



    Selected by Jacky G. Goetz

    Two contractile pools of actomyosin distinctly load and tune E-cadherin levels during morphogenesis

    Girish R. Kale, Xingbo Yang, Jean-Marc Philippe, et al.



    Selected by Arnaud Monnard

    Feedback control of neurogenesis by tissue packing

    Tom W. Hiscock, Joel B. Miesfeld, Kishore R. Mosaliganti, et al.



    Selected by Sarah Morson

    1

    Tunable molecular tension sensors reveal extension-based control of vinculin loading

    Andrew S LaCroix, Andrew D Lynch, Matthew E Berginski, et al.



    Selected by Amanda Haage

    1

    Also in the cell biology category:

    The cytoskeleton as a smart composite material: A unified pathway linking microtubules, myosin-II filaments and integrin adhesions

    Nisha Mohd Rafiq, Yukako Nishimura, Sergey V. Plotnikov, et al.



    Selected by Coert Margadant

    Quantitative, real-time, single cell analysis in tissue reveals expression dynamics of neurogenesis

    Cerys S Manning, Veronica Biga, James Boyd, et al.



    Selected by Teresa Rayon

    Profiling the surface proteome identifies actionable biology for TSC1 mutant cells beyond mTORC1 signaling

    Junnian Wei, Kevin K. Leung, Charles Truillet, et al.



    Selected by Rob Hynds

    1

    Optogenetic dissection of mitotic spindle positioning in vivo

    Lars-Eric Fielmich, Ruben Schmidt, Daniel J Dickinson, et al.



    Selected by Angika Basant

    1

    Excitable RhoA dynamics drive pulsed contractions in the early C. elegans embryo.

    Jonathan B Michaux, Francois B Robin, William M McFadden, et al.



    Selected by Sundar Naganathan

    Moving beyond P values: Everyday data analysis with estimation plots

    Joses Ho, Tayfun Tumkaya, Sameer Aryal, et al.



    Selected by Gautam Dey

    1

    A limited number of double-strand DNA breaks are sufficient to delay cell cycle progression.

    Jeroen van den Berg, Anna G. Manjon, Karoline Kielbassa, et al.



    Selected by Leighton Daigh

    Optogenetic manipulation of medullary neurons in the locust optic lobe

    Hongxia Wang, Richard B. Dewell, Markus U. Ehrengruber, et al.



    Selected by Ana Patricia Ramos

    JNK-mediated spindle reorientation in stem cells promotes dysplasia in the aging intestine

    Daniel Hu, Heinrich Jasper



    Selected by Maiko Kitaoka

    ER-to-Golgi trafficking of procollagen in the absence of large carriers.

    Janine McCaughey, Nicola Stevenson, Stephen Cross, et al.



    Selected by Gautam Dey

    1

    Template switching causes artificial junction formation and false identification of circular RNAs

    Chong Tang, Tian Yu, Yeming Xie, et al.



    Selected by Fabio Liberante

    Mechanosensitive binding of p120-Catenin at cell junctions regulates E-Cadherin turnover and epithelial viscoelasticity

    K. Venkatesan Iyer, Romina Piscitello-Gómez, Frank Jülicher, et al.



    Selected by Ivana Viktorinová

    Targeting light-gated chloride channels to neuronal somatodendritic domain reduces their excitatory effect in the axon

    Jessica Messier, Hongmei Chen, Zhao-Lin Cai, et al.

    AND

    High-efficiency optogenetic silencing with soma-targeted anion-conducting channelrhodopsins

    Mathias Mahn, Lihi Gibor, Katayun Cohen-Kashi Malina, et al.



    Selected by Mahesh Karnani

    2

    EFFECTORS OF THE SPINDLE ASSEMBLY CHECKPOINT BUT NOT THE MITOTIC EXIT NETWORK ARE CONFINED WITHIN THE NUCLEUS OF SACCHAROMYCES CEREVISIAE

    Lydia R Heasley, Jennifer G DeLuca, Steven M Markus



    Selected by Hiral Shah

    An atlas of the aging lung mapped by single cell transcriptomics and deep tissue proteomics

    Ilias Angelidis, Lukas M Simon, Isis E Fernandez, et al.



    Selected by Rob Hynds

    1

    Peculiar features of the plastids of the colourless alga Euglena longa and photosynthetic euglenophytes unveiled by transcriptome analyses

    Kristina Zahonova, Zoltan Fussy, Erik Bircak, et al.



    Selected by Ellis O'Neill

    1

    Close