Nav: Home

Elucidating cellular responses to force

March 07, 2019

Accumulated evidence suggests that physical force plays an important role in various developmental processes of fertilized animal eggs. During embryogenesis, a variety of cell populations actively migrate and change their positions, generating various types of force (e.g., traction force, compression force) that influence the properties of surrounding tissues. This in turn enables normal development where tissue arrangement is highly orchestrated. However, how embryonic cells and tissues respond to these forces remains poorly understood.

Tackling this important question was made possible by an international collaboration between two laboratories with expertise in proteomics and developmental biology. Professor Ileana Cristea from Princeton University (USA) and Professor Naoto Ueno from the National Institute for Basic Biology (Japan), along with their respective research groups, attempted to answer this question. Together, they characterized global phosphorylation and protein abundance intracellular changes in embryos to which physical force was applied.

"In this study, we applied force by centrifuging Xenopus embryos, and we extensively analyzed the changes in the phosphorylation state of proteins in them. Since Xenopus eggs are relatively larger than other organisms' eggs, we were able to obtain sufficient amounts of protein for the analysis from a small number of embryos." said Dr. Noriyuki Kinoshita, a member of the research team.

Using a sensitive and quantitative mass spectrometry-based approach, the research team was able to identify phosphorylations on over 9,000 peptides (i.e., fragments of proteins).

Prof. Cristea highlights the novelty and expected impact of this research by indicating that "This is the first study of global temporal alterations in protein phosphorylation in response to mechanical force in any biological system. We integrated methods that allowed us to globally characterize the dynamic phosphoproteome with targeted approaches that we designed to monitor the temporality and relative abundance of specific phosphorylation events with great accuracy. We further placed this knowledge of phosphorylation-mediated signaling in the context of protein abundance changes. Overall, this allowed us to discover precise modulatory points in response to force. Additionally, given the contribution of mechanical forces to both tissue homeostasis and progression of different diseases, we hope that our methods and findings will provide a valuable platform for future investigations in mechanobiology and signal transduction."

The first author of the paper, Dr. Hashimoto said, "It was interesting to note that a variety of protein kinases, such as PAK2 and PKC, in the embryo are activated by force stimulation for only 10 minutes. It was also surprising to find that proteins constituting focal adhesion and tight junctions were among those most prominently phosphorylated. This work also unveiled a previously unrecognized crosstalk between the FAK pathway and the PKA and PKC pathway. In addition, we have been able to demonstrate that centrifugation reinforces tight junctions, leading to the epithelialization of the tissue."

"In particular, it was intriguing to find that upon force stimulation, ZO-1 (one of the tight junction components) is accumulated to tight junctions to strengthen its structure, which is a characterictic of mesenchymal-epithelial transition (MET)-like change. This phenomenon is the opposite to epithelial-mesenchymal transition (EMT) found in some cells during development, wound healing, and cancer invasion/metastasis. We speculate that in embryos, there must be a feedback mechanism that enhances the robustness of tissues to resist deformations induced by force." Prof. Ueno said.

These results were published on March 6th, 2019 in the journal Cell Systems.
-end-
Cell Systems
"Mechanical Force Induces Phosphorylation-Mediated Signaling that Underlies Tissue Response and Robustness in Xenopus Embryos" by Yutaka Hashimoto, NoriyukiKinoshita, Todd M.Greco, Joel D.Federspiel, Pierre M.Jean Beltran, Naoto Ueno, Ileana M.Cristea
DOI: https://doi.org/10.1016/j.cels.2019.01.006

National Institutes of Natural Sciences

Related Protein Articles:

Hi-res view of protein complex shows how it breaks up protein tangles
A new, high-resolution view of the structure of Hsp104 (heat shock protein 104), a natural yeast protein nanomachine with six subunits, may show news ways to dismantle harmful protein clumps in disease.
Breaking the protein-DNA bond
A new Northwestern University study finds that unbound proteins in a cell break up protein-DNA bonds as they compete for the single-binding site.
FASEB Science Research Conference: Protein Kinases and Protein Phosphorylation
This conference focuses on the biology of protein kinases and phosphorylation signaling.
Largest resource of human protein-protein interactions can help interpret genomic data
An international research team has developed the largest database of protein-to-protein interaction networks, a resource that can illuminate how numerous disease-associated genes contribute to disease development and progression.
STAT2: Much more than an antiviral protein
A protein known for guarding against viral infections leads a double life, new research shows, and can interfere with cell growth and the defense against parasites.
A protein makes the difference
It is well-established knowledge that blood vessels foster the growth of tumors.
Nuclear protein causes neuroblastoma to become more aggressive
Aggressive forms of neuroblastoma contain a specific protein in their cells' nuclei that is not found in the nuclei of more benign forms of the cancer, and the discovery, made through research from the University of Rochester Medical Center, could lead to new forms of targeted therapy.
How a protein could become the next big sweetener
High-fructose corn syrup and sugar are on the outs with calorie-wary consumers.
High animal protein intake associated with higher, plant protein with lower mortality rate
The largest study to examine the effects of different sources of dietary protein found that a high intake of proteins from animal sources -- particularly processed and unprocessed red meats -- was associated with a higher mortality rate, while a high intake of protein from plant sources was associated with a lower risk of death.
Protein in, ammonia out
A recent study has compiled and analyzed data from 25 previous studies.

Related Protein Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Setbacks
Failure can feel lonely and final. But can we learn from failure, even reframe it, to feel more like a temporary setback? This hour, TED speakers on changing a crushing defeat into a stepping stone. Guests include entrepreneur Leticia Gasca, psychology professor Alison Ledgerwood, astronomer Phil Plait, former professional athlete Charly Haversat, and UPS training manager Jon Bowers.
Now Playing: Science for the People

#524 The Human Network
What does a network of humans look like and how does it work? How does information spread? How do decisions and opinions spread? What gets distorted as it moves through the network and why? This week we dig into the ins and outs of human networks with Matthew Jackson, Professor of Economics at Stanford University and author of the book "The Human Network: How Your Social Position Determines Your Power, Beliefs, and Behaviours".