TRPM7 triggers Ca2+ sparks and invadosome formation in neuroblastoma cells

Daan Visser, Michiel Langeslag, Katarzyna M Kedziora, Jeffrey Klarenbeek, Alwin Kamermans, F David Horgen, Andrea Fleig, Frank N van Leeuwen, Kees Jalink

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Cell migration depends on the dynamic formation and turnover of cell adhesions and is tightly controlled by actomyosin contractility and local Ca2+ signals. The divalent cation channel TRPM7 (Transient Receptor Potential cation channel, subfamily Melastatin, member 7) has recently received much attention as a regulator of cell adhesion, migration and (localized) Ca2+ signaling. Overexpression and knockdown of TRPM7 affects actomyosin contractility and the formation of cell adhesions such as invadosomes and focal adhesions, but the role of TRPM7-mediated Ca2+ signals herein is currently not understood. Using Total Internal Reflection Fluorescence (TIRF) Ca2+ fluorometry and a novel automated analysis routine we have addressed the role of Ca2+ in the control of invadosome dynamics in N1E-115 mouse neuroblastoma cells. We find that TRPM7 promotes the formation of highly repetitive and localized Ca2+ microdomains or "Ca2+ sparking hotspots" at the ventral plasma membrane. Ca2+ sparking appears strictly dependent on extracellular Ca2+ and is abolished by TRPM7 channel inhibitors such as waixenicin-A. TRPM7 inhibition also induces invadosome dissolution. However, invadosome formation is (functionally and spatially) dissociated from TRPM7-mediated Ca2+ sparks. Rather, our data indicate that TRPM7 affects actomyosin contractility and invadosome formation independent of Ca2+ influx.

Original languageEnglish
Pages (from-to)404-15
Number of pages12
JournalCell Calcium
Volume54
Issue number6
DOIs
Publication statusPublished - Dec 2013

Cite this

Visser, D., Langeslag, M., Kedziora, K. M., Klarenbeek, J., Kamermans, A., Horgen, F. D., ... Jalink, K. (2013). TRPM7 triggers Ca2+ sparks and invadosome formation in neuroblastoma cells. Cell Calcium, 54(6), 404-15. https://doi.org/10.1016/j.ceca.2013.09.003