TRPM7 triggers Ca2+ sparks and invadosome formation in neuroblastoma cells

Cell Calcium. 2013 Dec;54(6):404-15. doi: 10.1016/j.ceca.2013.09.003. Epub 2013 Oct 16.


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.

Keywords: 2-APB; 2-aminoethyl diphenylborinate; Adhesion; BK; Ca(2+) imaging; Ca(2+) signaling; ECM; FA; FC; Invadosome; TIRF; TIRF microscopy; TRPM7; Total Internal Reflection Fluorescence (microscopy); Transient Receptor Potential cation channel, subfamily Melastatin, member 7; bradykinin; extracellular matrix; focal adhesion; focal complex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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


  • Acetates
  • Diterpenes
  • RNA, Small Interfering
  • TRPM Cation Channels
  • waixenicin A
  • Actomyosin
  • Trpm7 protein, mouse
  • Calcium