Mechanotransduction coordinates extracellular matrix protein homeostasis promoting longevity in<i>C. elegans</i>

Teuscher, Alina C.; Statzer, Cyril; Goyala, Anita; Domenig, Seraina A.; Schoen, Ingmar; Hess, Max; Hofer, Alexander M.; Fossati, Andrea; Vogel, Viola; Göksel, Orçun; Aebersold, Ruedi; Ewald, Collin Y.

doi:10.1101/2022.08.30.505802

Cited by 4 publications

(1 citation statement)

References 154 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In C. elegans, yap-1 has previously been implicated in cell polarity 37,38 and in the regulation of aging 34,39 . However, a role for yap-1 in organ growth and size control of C. elegans , had not been characterized so far.…”

Section: Discussionmentioning

confidence: 99%

Ultra-sensitive coupling between organ growth and size by YAP-1 ensures uniform body plan proportions inC. elegans

Stojanovski

Gheorghe

Lanjuin

et al. 2022

Preprint

View full text Add to dashboard Cite

Imbalance between the growth rate of different organs can amplify to large deviations of their size proportions during development. We show that, for the C. elegans pharynx, such size divergence is prevented by reciprocal coordination of pharyngeal growth with other tissues. Live imaging of hundreds of individuals revealed that small pharynxes grow more rapidly than large pharynxes, catching up in volume during development. Moreover, pharynx-to-body size proportions were robust to even strong tissue-specific inhibition of mTORC1 and insulin signalling. Tissue-specific depletion of these pathways slowed-down the growth of the respective tissue and additionally triggered a systemic growth response that ensured appropriate organ size proportions. By mathematical modelling, we show that the conservation of proportions requires a bi-directional ultra-sensitive coupling of body growth and pharynx size that cannot be explained by a reduction of food uptake alone. Instead, organ growth coordination requires regulation by the mechano-transducing transcriptional co-activator YAP/yap-1. Knock-down of yap-1 makes animals sensitive to tissue-specific inhibition mTORC1 inhibition, causing a disproportionate pharynx and developmental arrest. Our data suggests that mechano-transduction tightly coordinates organ growth during C. elegans development to ensure the uniformity of body plan proportions among individuals.

show abstract

Section: Discussionmentioning

confidence: 99%

Ultra-sensitive coupling between organ growth and size by YAP-1 ensures uniform body plan proportions inC. elegans

Stojanovski

Gheorghe

Lanjuin

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

Maintenance of appropriate size scaling of the C. elegans pharynx by YAP-1

Stojanovski,

Gheorghe,

Lenart

et al. 2023

Nat Commun

View full text Add to dashboard Cite

Even slight imbalance between the growth rate of different organs can accumulate to a large deviation from their appropriate size during development. Here, we use live imaging of the pharynx of C. elegans to ask if and how organ size scaling nevertheless remains uniform among individuals. Growth trajectories of hundreds of individuals reveal that pharynxes grow by a near constant volume per larval stage that is independent of their initial size, such that undersized pharynxes catch-up in size during development. Tissue-specific depletion of RAGA-1, an activator of mTOR and growth, shows that maintaining correct pharynx-to-body size proportions involves a bi-directional coupling between pharynx size and body growth. In simulations, this coupling cannot be explained by limitation of food uptake alone, and genetic experiments reveal an involvement of the mechanotransducing transcriptional co-regulator yap-1. Our data suggests that mechanotransduction coordinates pharynx growth with other tissues, ensuring body plan uniformity among individuals.

show abstract

Strategic outline of interventions targeting extracellular matrix for promoting healthy longevity

Park

King²,

Björk³

et al. 2023

American Journal of Physiology-Cell Physiology

View full text Add to dashboard Cite

The extracellular matrix (ECM), composed of interlinked proteins outside of cells, is an important component of the human body that helps maintain tissue architecture and cellular homeostasis. As people age, the ECM undergoes changes that can lead to age-related morbidity and mortality. Despite its importance, ECM aging remains understudied in the field of geroscience. In this review, we discuss the core concepts of ECM integrity, outline the age-related challenges and subsequent pathologies and diseases, summarize diagnostic methods detecting a faulty ECM, and provide strategies targeting ECM homeostasis. To conceptualize this, we built a technology research tree to hierarchically visualize possible research sequences for studying ECM aging. This strategic framework will hopefully facilitate the development of future research on interventions to restore ECM integrity, which could potentially lead to the development of new drugs or therapeutic interventions promoting health during aging.

show abstract

Mechanotransduction coordinates extracellular matrix protein homeostasis promoting longevity inC. elegans

Cited by 4 publications

References 154 publications

Ultra-sensitive coupling between organ growth and size by YAP-1 ensures uniform body plan proportions inC. elegans

Ultra-sensitive coupling between organ growth and size by YAP-1 ensures uniform body plan proportions inC. elegans

Maintenance of appropriate size scaling of the C. elegans pharynx by YAP-1

Strategic outline of interventions targeting extracellular matrix for promoting healthy longevity

Contact Info

Product

Resources

About