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Cross-talk between the calcium channel TRPV4 and reactive oxygen species interlocks adhesive and degradative functions of invadosomes.

ABSTRACT: Invadosomes support cell invasion by coupling both acto-adhesive and extracellular matrix degradative functions, which are apparently antagonistic. β1-integrin dynamics regulate this coupling, but the actual sensing mechanism and effectors involved have not yet been elucidated. Using genetic and reverse genetic approaches combined with biochemical and imaging techniques, we now show that the calcium channel TRPV4 colocalizes with β1-integrins at the invadosome periphery and regulates its activation and the coupling of acto-adhesive and degradative functions. TRPV4-mediated regulation of podosome function depends on its ability to sense reactive oxygen species (ROS) in invadosomes' microenvironment and involves activation of the ROS/calcium-sensitive kinase Ask1 and binding of the motor MYO1C. Furthermore, disease-associated TRPV4 gain-of-function mutations that modulate ECM degradation are also implicated in the ROS response, which provides new perspectives in our understanding of the pathophysiology of TRPV4 channelopathies.

SUBMITTER: Vellino S

PROVIDER: S-EPMC7788461 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Cross-talk between the calcium channel TRPV4 and reactive oxygen species interlocks adhesive and degradative functions of invadosomes.

Vellino Sanela S Oddou Christiane C Rivier Paul P Boyault Cyril C Hiriart-Bryant Edwige E Kraut Alexandra A Martin René R Coute Yohann Y Knölker Hans-Joachim HJ Valverde Miguel A MA Albigès-Rizo Corinne C Destaing Olivier O

The Journal of cell biology 20210201 2

Invadosomes support cell invasion by coupling both acto-adhesive and extracellular matrix degradative functions, which are apparently antagonistic. β1-integrin dynamics regulate this coupling, but the actual sensing mechanism and effectors involved have not yet been elucidated. Using genetic and reverse genetic approaches combined with biochemical and imaging techniques, we now show that the calcium channel TRPV4 colocalizes with β1-integrins at the invadosome periphery and regulates its activat ...[more]

PMID: 33399853

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Project description:Ganoderma lucidum is among the best known medicinal basidiomycetes due to its production of many pharmacologically active compounds. To study the regulatory networks involved in its growth and development, we analyzed the relationship between reactive oxygen species (ROS) and Ca2+ signaling in the regulation of hyphal branching and ganoderic acid (GA) biosynthesis after Cu2+ treatment. Our results revealed that Cu2+ treatment decreased the distance between hyphal branches and increased the GA content and the intracellular levels of ROS and Ca2+ Further research revealed that the Cu2+-induced changes in hyphal branch distance, GA content, and cytosolic Ca2+ level were dependent on increases in cytosolic ROS. Our results also showed that increased cytosolic Ca2+ could reduce cytosolic ROS by activating antioxidases and modulating Cu2+ accumulation, resulting in feedback to adjust hyphal growth and GA biosynthesis. These results indicated that cytosolic ROS and Ca2+ levels exert important cross talk in the regulation of hyphal growth and GA biosynthesis induced by Cu2+ Taken together, our results provide a reference for analyzing the interactions among different signal transduction pathways with regard to the regulation of growth and development in other filamentous fungi.IMPORTANCEGanoderma lucidum, which is known as an important medicinal basidiomycete, is gradually becoming a model organism for studying environmental regulation and metabolism. In this study, we analyzed the relationship between reactive oxygen species (ROS) and Ca2+ signaling in the regulation of hyphal branching and ganoderic acid (GA) biosynthesis under Cu2+ stress. The results revealed that the Cu2+-induced changes in the hyphal branch distance, GA content, and cytosolic Ca2+ level were dependent on increases in cytosolic ROS. Furthermore, the results indicated that increased cytosolic Ca2+ could reduce cytosolic ROS levels by activating antioxidases and modulating Cu2+ accumulation. The results in this paper indicate that there was important cross talk between cytosolic ROS and Ca2+ levels in the regulation of hyphal growth and GA biosynthesis induced by Cu2.

Dataset Information

Cross-talk between the calcium channel TRPV4 and reactive oxygen species interlocks adhesive and degradative functions of invadosomes.

Publications

Cross-talk between the calcium channel TRPV4 and reactive oxygen species interlocks adhesive and degradative functions of invadosomes.

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