TRPV4 mediates the Ca2+ influx required for the interaction between flightless-1 and non-muscle myosin, and collagen remodeling

Journal of Cell Science
Pamma D AroraChristopher A McCulloch

Abstract

Fibroblasts remodel extracellular matrix collagen, in part, through phagocytosis. This process requires formation of cell extensions, which in turn involves interaction of the actin-binding protein flightless-1 (FliI) with non-muscle myosin IIA (NMMIIA; heavy chain encoded byMYH9) at cell-matrix adhesion sites. As Ca2+plays a central role in controlling actomyosin-dependent functions, we examined how Ca2+controls the generation of cell extensions and collagen remodeling. Ratio fluorimetry demonstrated localized Ca2+influx at the extensions of fibroblasts. Western blotting and quantitative (q)PCR showed high expression levels of the Ca2+-permeable transient receptor potential vanilloid-4 (TRPV4) channel, which co-immunoprecipitated with β1 integrin and localized to adhesions. Treatment with α2β1-integrin-blocking antibody or the TRPV4-specific antagonist AB159908, as well as reduction of TRPV4 expression through means of siRNA, blocked Ca2+influx. These treatments also inhibited the interaction of FliI with NMMIIA, reduced the number and length of cell extensions, and blocked collagen remodeling. Pulldown assays showed that Ca2+depletion inhibited the interaction of purified FliI with NMMIIA filaments. Fluorescence resonance ene...Continue Reading

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Citations

Aug 10, 2018·Molecular Biology of the Cell·P D AroraC A McCulloch
Oct 12, 2019·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·M Rocio Servin-VencesAnca Margineanu
Jul 10, 2020·Journal of Cellular Physiology·Kei NakajimaChristopher A McCulloch
Jan 25, 2019·Proceedings of the National Academy of Sciences of the United States of America·Christopher L GilchristFarshid Guilak
Mar 27, 2020·Frontiers in Immunology·Laura Michalick, Wolfgang M Kuebler
Jun 7, 2020·Experimental & Molecular Medicine·Sun Sil ChoiJang Hyun Choi
Jul 12, 2020·Journal of Cell Science·Pardis PakshirBoris Hinz
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Dec 18, 2020·Frontiers in Cell and Developmental Biology·Xanthe L Strudwick, Allison J Cowin
Apr 1, 2021·American Journal of Physiology. Cell Physiology·Monika Lakk, David Križaj
May 14, 2021·Frontiers in Molecular Biosciences·Liangliang LiuTingting Zhou
Aug 7, 2021·Biomolecules·Tytti Kärki, Sari Tojkander

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