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TRPV4 participates in the establishment of trailing adhesions and directional persistence of migrating cells

  • Ion channels, receptors and transporters
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Pflügers Archiv - European Journal of Physiology Aims and scope Submit manuscript

Abstract

Calcium signaling participates in different cellular processes leading to cell migration. TRPV4, a non-selective cation channel that responds to mechano-osmotic stimulation and heat, is also involved in cell migration. However, the mechanistic involvement of TRPV4 in cell migration is currently unknown. We now report that expression of the mutant channel TRPV4-121AAWAA (lacking the phosphoinositide-binding site 121KRWRK125 and the response to physiological stimuli) altered HEK293 cell migration. Altered migration patterns included periods of fast and persistent motion followed by periods of stalling and turning, and the extension of multiple long cellular protrusions. TRPV4-WT overexpressing cells showed almost complete loss of directionality with frequent turns, no progression, and absence of long protrusions. Traction microscopy revealed higher tractions forces in the tail of TRPV4-121AAWAA than in TRPV4-WT expressing cells. These results are consistent with a defective and augmented tail retraction in TRPV4-121AAWAA- and TRPV4-WT-expressing cells, respectively. The activity of calpain, a protease implicated in focal adhesion (FA) disassembly, was decreased in TRPV4-121AAWAA compared with TRPV4-WT-expressing cells. Consistently, larger focal adhesions were seen in TRPV4-121AAWAA compared with TRPV4-WT-expressing HEK293 cells, a result that was also reproduced in T47D and U87 cells. Similarly, overexpression of the pore-dead mutant TRPV4-M680D resumed the TRPV4-121AAWAA phenotype presenting larger FA. The migratory phenotype obtained in HEK293 cells overexpressing TRPV4-121AAWAA was mimicked by knocking-down TRPC1, a cationic channel that participates in cell migration. Together, our results point to the participation of TRPV4 in the dynamics of trailing adhesions, a function that may require the interplay of TRPV4 with other cation channels or proteins present at the FA sites.

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Acknowledgments

This work was supported by grants from the Spanish Ministry of Economy and Competitiveness (SAF2012-38140 and BFU2012-38146), FEDER Funds, Fondo de Investigación Sanitaria (Red HERACLES RD12/0042/0014), Generalitat de Catalunya (2014SGR20) and European Research Council (grant Agreement 242993).

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Laboratory of Molecular Physiology and Channelopathies, Dept. of Experimental and Health Sciences, Universitat Pompeu Fabra, C/ Dr. Aiguader 88, Barcelona, 08003, Spain

    Sanela Mrkonjić, Anna Garcia-Elias, Carlos Pardo-Pastor, Rubén Vicente & Miguel A. Valverde

  2. Institute for Bioengineering of Catalonia, Barcelona, Barcelona, Spain

    Elsa Bazellières & Xavier Trepat

  3. Facultat de Medicina, Universitat de Barcelona, and Ciber Enfermedades Respiratorias, Barcelona, Barcelona, Spain

    Elsa Bazellières & Xavier Trepat

  4. Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Barcelona, Spain

    Xavier Trepat

  5. Laboratory of Ion Channels and TRP Research Platform Leuven, KU Leuven, Leuven, Belgium

    Joris Vriens, Debapriya Ghosh & Thomas Voets

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  1. Sanela Mrkonjić
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  2. Anna Garcia-Elias
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  3. Carlos Pardo-Pastor
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  4. Elsa Bazellières
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  5. Xavier Trepat
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  6. Joris Vriens
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  7. Debapriya Ghosh
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  8. Thomas Voets
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  9. Rubén Vicente
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  10. Miguel A. Valverde
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Correspondence to Miguel A. Valverde.

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S.M and A.G-E. contributed equally to this work.

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Mrkonjić, S., Garcia-Elias, A., Pardo-Pastor, C. et al. TRPV4 participates in the establishment of trailing adhesions and directional persistence of migrating cells. Pflugers Arch - Eur J Physiol 467, 2107–2119 (2015). https://doi.org/10.1007/s00424-014-1679-8

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  • DOI: https://doi.org/10.1007/s00424-014-1679-8

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