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

57 Citations (Scopus)


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
Issue number6
Publication statusPublished - Dec 2013


  • Acetates/pharmacology
  • Actomyosin/metabolism
  • Animals
  • Calcium Signaling
  • Calcium/metabolism
  • Cell Adhesion/drug effects
  • Cell Line, Tumor
  • Cell Membrane/metabolism
  • Cell Movement/drug effects
  • Diterpenes/pharmacology
  • Mice
  • Neuroblastoma/metabolism
  • RNA Interference
  • RNA, Small Interfering/metabolism
  • TRPM Cation Channels/antagonists & inhibitors

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